Uses of a nucleic acid molecule and compositions comprising the same for the treatment of an inflammatory disorder.

Abstract

MOLECULE FOR TREATING AN INFLAMMATORY DISORDER The invention provides a source of L19 as a medicament, preferably for the prevention or treatment of an inflammatory disorder in an individual.

Description

Descriptive Report of the Invention Patent for: USES OF A NUCLEIC ACID MOLECULE AND COMPOSITIONS COMPRISING THE SAME FOR THE TREATMENT OF AN INFLAMMATORY DISORDER Field of invention The invention provides a source of L19 as a medicine, preferably for the prevention or treatment of an inflammatory disorder in an individual. Background of the invention Immunological and inflammation-related diseases are a manifestation of complex, often interconnected biological pathways that, in normal physiology, respond to an insult or injury by initiating repair of the insult or injury and mounting an innate and acquired response. Disease or pathology occurs when these physiological pathways cause further insult or injury due to an exaggerated response caused by abnormal regulation or overstimulation, or a combination of both. Despite the advent of new anti-inflammatory drugs, such as anti-TNF agents, inflammatory diseases continue to represent a significant unmet medical need, often due to unresponsiveness and resistance to these medications. Immunological and inflammation-related diseases that can be modulated by the use of anti-inflammatory agents include autoimmune diabetes (any other similar condition), diabetes mellitus, uveitis, (1) multiple sclerosis, arthritis Petition 870220005364, dated 21 / 01 / 2022, page 10 / 14 rheumatoid (RA), irritable bowel disease (IBD), irritable bowel syndrome, ulcerative oolitis, Crohn's disease, control of allograft rejection after organ transplantation, graft-versus-host disease (GVHD), inflammatory lung diseases including asthma and chronic obstructive pulmonary disease (COPD) (2), cancer (4) systemic lupus erythematosus, SLE, sarcoidosis, cancer and psoriasis. Rheumatoid arthritis (RA) is considered a systemic autoimmune disease, managed by treatment with disease-modifying antirheumatic drugs (DMARDs), typically in combination, to minimize the side effects associated with systemic drugs. Side effects of these drugs include ulcerative stomatitis and reduced white blood cell count. IBD is a term that describes a chronic inflammatory disorder of the small and / or large intestine. Crohn's disease and ulcerative colitis are included within the scope of IBD. Although the exact causes are not fully established, IBD is considered an autoimmune disease. Currently, there is no cure, and treatments focus on suppressing the abnormal or exaggerated inflammatory response. Treatments include corticosteroids (such as methotrexate, azathioprine, and mercaptopurine) and aminosalicylates. Prolonged use of corticosteroids is associated with bone weakening, infection, cataracts, and effects on bone and bone marrow. Aminosalicylates tend to be better tolerated, as they are poorly absorbed and act topically on the affected area. Side effects include headache and, rarely, more serious conditions such as pancreatitis, Psoriasis is treated in different ways. The use of topical corticosteroids is a common treatment method, but its disadvantages include ineffectiveness and the development of resistance. Phototherapy is effective in treating psoriasis by increasing apoptosis, which is implicated in reduced inflammation. Short-term disadvantages are increased discomfort and itching, and long-term effects include a higher risk of squamous cell carcinoma and melanoma skin cancers. Systemic drugs are used to treat psoriasis, which have a variety of other systemic, often undesirable, effects and should be used under the supervision and monitoring of a dermatologist. Therefore, there is still a need to devise new treatments for inflammatory diseases such as rheumatoid arthritis (RA), intermittent hemorrhoids (IBD), and psoriasis that do not have all the disadvantages of existing treatments. Description of the Invention LI9 Source In one aspect, a source of L19 is provided for use as a medicine. L19 is a ribosomal protein. Cytosolic ribosomal proteins are well conserved. Therefore, it is a source of L19 can be prepared from any eukaryotic organism, whether plant or animal, be it mammalian, reptile, fish, insect, or any other organism with a chromosome, such as protozoa. The invention is not limited to a specific source of L19, provided that the encoded L19 protein product is capable of inducing an anti-inflammatory response, as defined further in this document. Preferred protozoa include Plasmodium and, particularly, members of the trypanosome family, more specifically different species of the protozoan trypanosome Leishmania. There are more than 20 known species of Leishmania, including species of the subgenus Leishmaniàj comprising the L. major complex, including L. major, or pomegranate L. Donovani, including L. chagasi, L . donovani and L. infantum , the L. mexicana complex including L . The L19 source can be obtained from a trypanosome species. A trypanosome species can be Trypanosoma cruzi or Trypanosoma brucei. In a preferred embodiment, an L19 source is obtained from, derived from, or originating from a Leishmania species, preferably Leishmania major, Leishmania infantum, Leishmania donovani, Leishmania chagasi, and / or Leishmania braziliensis. It is more preferably a source of L19 that is obtained from, derived from, or originating from Leishmania major. The L19 subspecies of Plasmodium amazonensis and L. mexicana, as well as the Viannia subspecies, comprising the L. braziliensis complex, including L. braziliensis and L. peruviana, and the L. guyanensis complex, including L. guyanensis and L. panamensis. Plasmodium falciparum and Plasmodium vivax are species of Plasmodium of particular interest. Alternatively, an L19 source can be obtained from a trypanosome species. A trypanosome species can be Trypanosoma cruzi or Trypanosoma brucei.A person skilled in the art will understand that an L19 source can also be prepared by mixing two or more L19 sources derived from the same organism or from several different organisms, as identified in this document. The use of an L19 source has been shown in this document to have attractive properties, since the encoded L19 protein product has been demonstrated to be capable of inducing an anti-inflammatory response in a treated individual. A preferred source of L19 is a nucleic acid molecule, an oligonucleotide, a protein, a protein fragment, and / or a peptide, each derived from an L19 protein, polypeptide, or nucleic acid molecule, as defined in this document. A preferred source of L19 comprises or consists of an L19 oligopeptide protein, an L19-derived peptide, or a... L19, a protein fragment, L19, a nucleic acid molecule encoding an L19 protein, L19 polypeptide or L19-derived peptide, or an L19 protein fragment, each as defined in this document. A preferred L19 protein is represented by SEQ ID No: 1. This protein L19 preference is preferentially encoded by SEQ ID. Node: 2. Another preferred L19 protein is represented by SEQ ID No: 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or Each of these other L19 proteins is preferentially encoded by the SEQ ID No: 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 30, respectively. In a first scenario, a preferred source of LI 9 is a nucleotide sequence molecule, a nucleic acid sequence selected from the nucleotide polypeptide comprising a group that encodes amino acids in: one that has at least 50% identity or sequence similarity to the amino acid sequence of SEQ ID. Nos: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, or 29, ii. nucleotide sequences that comprise at least one nucleotide sequence 50% sequence identity or similarity with the nucleotide sequences of SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30, iii. nucleotide sequences whose complementary strand hybridizes with a nucleic acid molecule of sequence (i) or (ii), and iv. nucleotide sequences which differ from the sequence of a nucleic acid molecule of (iii) due to the degeneracy of the genetic code. In a second embodiment, a preferred source of L19 is a polypeptide encoded by a nucleic acid molecule of the first embodiment, as identified above. In a more preferred embodiment, a source of L19 is a polypeptide whose amino acid sequence has at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99%, or 100% sequence identity or similarity to a polypeptide having the amino acid sequence SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, or 31. Several L19 proteins and corresponding coding nucleic acid molecules have been identified. Each of these L19 proteins comprises an amino acid sequence with at least 60%, 70 80%, 90%, 95% or more with SEQ ID No: 1. Each of the nucleic acid molecules that codes for each of these proteins has at least one SEQ ID. No: 2. Each one LI 9 60% comprises a sequence 70%, 80%, 90%, 95% or more of these L19 proteins represent a homolog of the L19 protein from Leishmania major, as represented by SEQ ID No: 1. In summary, three L19 proteins from Leishmania braziliensis were identified, represented by the SEQ IDs. Nos: 5, 7, or 9. Each of these proteins is preferentially encoded by the following nucleotide sequences. SEQ ID Nos: 6, 8 or 10 respectively. Two proteins were also identified. LI 9 of Leishmania infantum, represented by the SEQ ID Nos: or 13. coded Each of these proteins is preferentially bound by the following nucleotide sequence SEQ ID Nos: or 14 respectively. Two proteins were also identified. LI 9 of Leishmania mexicana, being represented by the SEQ ID Nos: or 17. Each of these proteins is preferentially encoded by the following nucleotide sequence SEQ ID Nos: or 18 respectively. A protein L19 from Leishmania donovani was also identified, [represented by SEQ ID No: 19. This protein is preferentially encoded by the following nucleotide sequence SEQ ID NO: 20. In addition, four L19 proteins from Trypanosoma cruzi were identified, represented by SEQ ID Nos: 21, 23, 25 or 27. Each of these proteins is preferentially encoded by the following nucleotide sequences SEQ ID Nos: 22, 24, 26 or 28 respectively. A Trypanosoma brucei Ll9 protein was also identified, represented by SEQ ID No: 29. This protein is preferentially encoded by the following nucleotide sequence SEQ ID NO: 30. Preferably, said amino acid sequence or nucleotide sequence, as defined in this document, having at least 50% identity or similarity to a specifically identified amino acid or nucleotide sequence, is encompassed by the present invention and is considered functional when the encoded protein polypeptide, protein fragment or peptide is capable of inducing an anti-inflammatory response, as obtained by the L;19 protein represented by SEQ ID No: 15, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 29 to at least some degree. At least some degree means preferably at least 50%, at least 60%, 70%, 80%, at least 90% or 100% of the anti-inflammatory response induced by SEQ ID No: 1, 5, 7, 9, 11, [13, 15, 17, 19, 21, 23, 25, 27 or 29. Induction of an anti-inflammatory response is, or is preferably defined as, the ability to induce a detectable production of an anti-inflammatory compound and / or the ability to induce a decrease in the production of an inflammatory compound in a treated subject or individual. An anti-inflammatory compound is preferably a cytokine. The most preferred inflammatory cytokine is IFNγ and / or TNFα. IL-10. A cytokine compound. The cytokine The production of IL-10, IFNγ or TNFα is preferably evaluated at the mRNA level using PCR or at the protein level using ELISA, an ELISPOT, or FACS. (All of these techniques are known to those skilled in the art. Many publications involve the elevation of IL-10 with a decrease in inflammation as a result of the disease. The same occurs with the elevation of IFNγ or TNFα, and with the occurrence of inflammation.) The production of an anti-inflammatory compound can be evaluated in a treated individual or in a sample obtained from said individual. In this context, a sample can be a tissue, a fluid, or a cell. Preferred tissue includes spleen, skin, intestine, or lung. Preferred fluid includes blood. Preferred cells include PEMC (peripheral blood mononuclear cells), epithelial cells, intestinal cells, or lung cells. An anti-inflammatory response can be induced after at least 1, 2, 3, 4, 5, 6, or 7 days of treatment with an L19 source.The preferred sources of L19 are a polypeptide, protein, protein fragment, or L19 peptide. Induction of an anti-inflammatory response can also be an increase in the amount or quantity of IFNγ. In this context, an increase can mean an increase of at least 1%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 100%. Induction of an anti-inflammatory response can also be a decrease in the amount or quantity of IFNγ and / or... TNFa. In this context, a decrease could mean a reduction of at least 1 5%, 10% 25% 30% 35%, 40%, 45 55%, 60%, 65%, 70%, 80%, 85% 90% 95% or 100 In a preferred embodiment, an anti-inflammatory compound is produced and no detectable inflammatory compound (i.e., IFNγ and / or TNFα) is detected. In this context, no IFN-γ and / or TNFα is detected. The absence of TNFα and / or IFN-γ is preferably assessed using PCR or ELISA. The absence of an inflammatory compound can be assessed in a treated individual or in a sample obtained from said individual, as for the anti-inflammatory compound. In a preferred assay, an anti-inflammatory response, most preferably IL-10 production or an increase in IL-10, is detected after at least 24, 48, or 72 hours of incubation of an L19 source, preferably an L19 polypeptide or a peptide. L19 with PBMC. In this preferred assay, a small amount of IFN-gamma and / or a small amount of TNF-α or absence of detectable IFN-γ and / or TNF-α is detected after at least 24, 48, or 72 hours of incubation of an L19 source, preferably an L19 polypeptide or an L19 peptide with PBMC. More preferably, IL-10, IFN-γ, and / or TNF-α is evaluated by ELISA, as described in the experimental part. In another preferred embodiment, an L19 source that is capable of inducing an anti-inflammatory response is also capable of preventing and / or delaying the development of an inflammatory disorder, condition, or disease, and / or is capable of alleviating one or more symptom(s). I and / or one or more characteristic(s) or parameter(s) of a cell or tissue of an individual treated as defined further in this document. A preferred LI9 source is a nucleic acid molecule of the first embodiment, as identified above. This preferred nucleic acid molecule is represented by a nucleotide sequence that is derived from SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 OR 30, or a sequence with at least 50% identity or similarity to SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30, or a portion thereof, and which may include substitutions, insertions, deletions and additional 5' and / or 3' terminal nucleotides or chemical moieties to increase stability, solubility or bleaching.In a preferred embodiment, a source of L19 is a nucleic acid molecule whose nucleotide sequence has at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, [58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, [70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, [82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, [94%, 95%, 96%, 97%, 98%, 99% or 100% sequence identity or similarity with SEQ ID No: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30, or with a part thereof. An L19 nucleic acid molecule, as defined in this document, is preferably an oligonucleotide. A preferred oligonucleotide has a length of at least 8, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 nucleotides and is derived from SEQ ID No: 2, k, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, or 30. More preferred oligonucleotides comprise at least 8, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more contiguous nucleotides of a corresponding L19 nucleic acid molecule, as identified above, preferably represented by SEQ ID No: 2, 4, b, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 OR 30 and whose encoded product is capable of inducing an anti-inflammatory response, as previously defined in this document.In a preferred embodiment, therefore, a nucleic acid molecule L19, as defined in this document, is preferably an oligonucleotide comprising at least 8, 10, 15, 20, 25, 30, 35, 40, 45, 50,. 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more contiguous nucleotides of SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 or 30. Therefore, a preferred source of L19 is an oligonucleotide comprising at least 8, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more contiguous nucleotides of SEQ ID No: 2. Another preferred source of L19 is a polypeptide encoded by a nucleic acid molecule of the first embodiment, as identified above, and / or is a polypeptide whose amino acid sequence has at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97% 98%, 99% oil, 100% sequence identity or similarity to a polypeptide having the amino acid sequence SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 29, or a part thereof. A preferred polypeptide is represented by an amino acid sequence that is derived from SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 29, or one part of the sequence, or a sequence with at least 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity or similarity with SEQ ID NO: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 29, or a part thereof, and which may include substitutions, insertions, deletions and additional N- or C-terminal amino acids or chemical moieties to increase stability, solubility. An L19 protein fragment, an L19-derived peptide, an L19 polypeptide, or an L19 protein, as defined in this document, is preferably a fragment comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 265 or 267 contiguous amino acids of a corresponding L19 protein, preferably represented by SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 or 29, and capable of inducing an anti-inflammatory response as previously defined in this document. In a preferred embodiment, therefore, an L19 protein fragment or an L19-derived peptide, as defined in this document, is preferably a fragment comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 265 or 267 contiguous amino acids of SEQ ID n°: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29. A source of L19 may also comprise a full-length L19 protein, such as that represented by SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29, and comprises additional amino acids at the N- and / or C-terminus of the L19 protein. In another preferred embodiment, an L19 source comprises or consists of a protein or a polypeptide comprising at least one protein fragment of an L19 protein. A preferred L19 source is a protein fragment comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 3θ), 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41,42, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 265 or 267 contiguous amino acids of SEQ ID No: 1. In one embodiment, a source of L19 is a peptide derived from SEQ ID No: 1 or a fragment of SEQ ID No: 1. A preferred fragment or peptide comprises at least 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, or 42 contiguous amino acids from SEQ ID No: 1. In Example 3, three regions of L19 and specific peptides derived from L19 were identified as being capable of inducing the production of IL-10. The preferred regions for L19 are as follows: Region 1 comprises peptides with SEQ ID No: 31, 32 and / or 55, Region 2 comprises peptides with SEQ ID No: 42, 43, and / or 56 Region 3 comprises peptides with SEQ ID No: 53, 54 and / or 57. Below we define in more detail these peptides or fragments of SEQ ID No: 1. A protein fragment of SEQ ID No: 1 comprising at least 14 contiguous amino acids of the SEQ ID No: 1 and including SEQ ID Nos: 31, 32, 55, 42, 43, 44, 56, 53, 54 and / or 57. A more preferred fragment of SEQ ID No: 1 includes up to 40, 39 SEQ ID NO: 31, 32, 42, 43, 44, 38, 37, 36, 35, 34, 33, 32, or 53, and includes 31, 30, 29, 28, 27, 26, Node: 42, , , 25, 24 23, 22, 21, or 20 contiguous amino acids of the SEQ ID 1. The said fragment may comprise SEQ ID 43, 44 37, 36 22, NODE: 31, 32, or 53, and 35, 34, or it can have a length of 33, 32, 31, 30, 29, 28, 27 amino acids. The said preferably consists of SEQ ID NO: 31, up to 40, 39, 32, 26, 25, 24, fragment 42, 43, 44 or 53. Another understands 36, 21, SEQ 35, 34 most preferred fragment of SEQ ID No: 1 a SEQ ID , 33, 32, 20, 19, 18, 17, Node: 31, 16, and includes up to 30, 29, 28, 27, 26, ID No: and can 40, 39, 38, 37, 25, 24, 23, 22, or 14 contiguous amino acids of 1. The said fragment may have a length of up to 40, 39, 34, 33, 32 19, 18, 1 a SEQ ID 37, 36, NODE: 35, 31, 30, 29, 28, 27, 26, 25, 24, 7, 16, 15 or 14 amino acids. Preferably consists of SEQ ID NO: 54. A more preferred fragment of 23, 22, 21, 20, said fragment SEQ ID No: 1 includes) SEQ ID Node: and includes up to 40 39, 38, 37, 36, 35, 34 33, 32, 31, 30, 29, 28, 27, 26 or 25 contiguous amino acids from SEQ ID No: 1. Said fragment may comprise SEQ ID No: 57 and may have a length of up to 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26 or 25 amino acids. Said fragment preferably consists of SEQ ID NO: 57. A more preferred fragment of SEQ ID No: 1 comprises SEQ ID No: 55 and comprises up to 40, 39, 38, 37, 36, 36, 35, 34, 33, 32 or 31 contiguous amino acids of SEQ ID No: 1. The said fragment may comprise SEQ ID No: 55 and may have a length of up to 40, 39, 38, 37, 36, 35, 34, 33, 32 or 31 amino acids. The said fragment preferably consists of SEQ ID NO: 55. A more preferred fragment of SEQ ID No:l comprises SEQ ID No: 56 and comprises up to 50, 49, 48, 47, 46, 45, 44, 43 or 42 contiguous amino acids of SEQ ID No: 1. The said fragment may comprise SEQ ID No: 56 and may have a length of up to 50, 49, 48, 47, 46, 45, 44, 43 or 42 amino acids. The said fragment preferably consists of SEQ ID NO: 56. Each of the preferred fragments of SEQ ID No: 1, 20 as identified in this document, is preferentially capable of inducing an anti-inflammatory response as defined earlier in this document. The source of L19 may be a protein, a protein digest, and / or a fragment thereof, which may be in a purified form or may be comprised within a crude composition, preferably of biological origin, such as a bacterial lysate, yeast lysate, fungal lysate, bacterial supernatant, yeast supernatant, fungal supernatant, sonicate, or fix. Alternatively, a source of L19 may be chemically synthesized or enzymatically produced in vitro, in a cell-free system, or in a cellular system. The source of an L19 protein or fragment thereof may also be a nucleic acid encoding it, or a fragment thereof, from an RNA or DNA template. The RNA or DNA molecules may be naked DNAs, preferably comprised in vesicles or liposomes, or they may be comprised in a vector.The vector may be any DNA or RNA (recombinant) vector known in the art, and preferably a plasmid; wherein genes encoding latency antigens are operably linked to regulatory sequences that confer expression and translation of the encoded messengers. The vector may also be a DNA or RNA virus, such as, but not limited to, adenovirus, adeno-associated virus (AAV), a retrovirus, a lentivirus, modified vaccinia ankara virus (MVA), or avian pox virus, or any other viral vector capable of conferring expression of said polypeptide to a selected individual. DNA vectors may be non-integrating, such as episomally replicating vectors, or they may be integrating vectors in the host genome by random integration or homologous recombination. A source of L19 or a composition as defined in this document for use in accordance with the invention may be suitable for in vitro administration to a cell, tissue, or organ of individuals affected by or at risk of developing an inflammatory disorder, may be suitable for in vivo or ex vivo administration to a cell, tissue, and / or organ of such individuals, and / or may be appropriate for in vivo administration to such individuals. Depending on the type of source used (protein-based or nucleic acid-based), a person skilled in the art will know which type of formulation is suitable. A source of L19 may be administered as such (nude nucleic acid or protein). Alternatively, a nucleic acid-based source may be administered using nucleic acid constructed from L19 or as defined in this document.The said source, a composition as defined in this document, may be directly or indirectly administered in vivo, j in vitro or ex vivo to a cell, tissue and / or organ of an individual affected by or at risk of developing an inflammatory disorder, or in vivo to such individual. Preferably, said cells are cells from an individual suffering from an inflammatory disorder. Preferably, said tissue is a tissue from an individual suffering from an inflammatory disorder. Depending on the inflammatory disorder, a particular type of cell or tissue may be more suitable for treatment with a source of L19 or a composition of the invention. For example, a tissue may be skin, blood, intestine, lung, and suitable cells may be derived from these tissues. A source of L19 or a composition of the invention may be indirectly administered using suitable means known in the art. A nucleic acid molecule, as defined in a first embodiment, may, for example, be supplied to an individual or a cell, tissue or organ of said individual in the form of an expression vector wherein the expression vector encodes a transcript comprising said nucleic acid molecule. The expression vector is preferably introduced into a cell, tissue, organ or individual via a gene delivery vehicle. In a preferred embodiment, a viral-based expression vector comprising an expression cassette or a transcription cassette that drives the expression or transcription of a molecule, as identified in this document, is provided. A preferred delivery vehicle is a viral vector, such as an adeno-associated virus (AAV) vector, or a retroviral vector, such as a lentivirus vector and the like. Also, plasmids, artificial chromosomes, suitable plasmids for targeted homologous recombination and integration into the human genome of cells can be properly applied for the administration of the nucleic acid molecule as defined in a first embodiment. Improvements in means of delivering to an individual I or a cell, tissue, organ of said individual a source of L19 or a composition as defined in this document are anticipated, considering the progress that has been achieved to date. When administering a source of L19 or a composition, it is preferable that said source of L19 or composition be dissolved in a solution that is compatible with the delivery method. For intravenous, subcutaneous, intramuscular, intradermal, intrathecal and / or intraventricular administration, it is preferable that the solution be a physiological saline solution. In the context of the invention, a subject, an individual, a patient, or an animal means a human being or an animal. An animal that falls within the scope of the invention includes a mammal. Preferred mammals include a dog and a cat. In a preferred embodiment, at least 1 pg of an L19 source is used to induce an anti-inflammatory response. The L19 source dose ranges, as provided above, are preferred doses for in vitro or ex vivo uses. Those skilled in the art will understand that depending on the L19 source used, the cell, tissue, organ, or individual to be treated, the medium used, and the transfection and incubation conditions, the dose of the L19 source used may vary further and additional optimization may be necessary. A source of L19 is preferably a medicine or for use as a medicine. More preferably, said medicine is for preventing, delaying and / or treating an inflammatory disorder in an individual in need thereof. Within the context of the invention, an inflammatory disorder is any inflammatory disease or condition, or any condition in which inflammation will occur at a certain stage.Examples of inflammatory diseases or conditions include, but are not limited to, rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease (IBD) (including Crohn's disease or ulcerative colitis), irritable bowel syndrome, hepatitis, sepsis, alcoholic liver disease and non-alcoholic fatty liver disease, nephritis, such as glomerular nephritis, asthma, endocarditis, myasthenia gravis, multiple sclerosis, autoimmune diabetes (any other similar diabetes mellitus), uveitis, (1) control of allograft rejection after organ transplantation, graft-versus-host disease (GVHD), inflammatory lung diseases including asthma and chronic obstructive pulmonary disease (COPD) (2), cancer (4) systemic lupus erythematosus, SLE, sarcoptic mange, UV-induced skin inflammation, atopic dermatitis and sarcoidosis. As used in this document, the term hepatitis refers to a gastrointestinal disease, condition, or disorder characterized, at least in part, by inflammation of the liver. Examples of hepatitis include, but are not limited to, hepatitis associated with the hepatitis C virus. A, hepatitis B virus, hepatitis C virus, or liver inflammation associated with ischemia / reperfusion. In a more preferred embodiment, said medicament is capable of alleviating one or more symptom(s) of a treated patient and / or one or more characteristic(s) or parameter(s) of a cell, tissue or organ of a treated patient are improved using a source of L19 or a composition of the invention. For each inflammatory disease, a person skilled in the art knows at least one symptom, parameter or characteristic, values ​​of said parameter or characteristic associated with said disease and how to evaluate each of them. If a medicinal product of the invention is capable of inducing an anti-inflammatory response, as previously defined in this document, said medicinal product is also considered capable of preventing and / or delaying the development of an inflammatory disorder, condition or disease and / or improving one or more characteristic(s) or parameter(s) of a cell or tissue of a treated individual, as defined further in this document. Below, we provide a specific parameter for rheumatoid arthritis, psoriasis, and inflammatory bowel disease, respectively. Rheumatoid arthritis is a systemic disease and one of the most common forms of arthritis. It is characterized by inflammation of the membrane lining the joint, causing pain, stiffness, heat, redness, and swelling. There are several known animal models for AR in the field. One example is the collagen-induced arthritis (CIA) model, in which mice develop chronic inflammatory arthritis that closely resembles human rheumatoid arthritis. Since CIA shares similar immunological and pathological characteristics with... RA, this makes it a suitable model for potential analysis treatments for FROG. In this model, the basic mechanisms of pathogenesis are known, with the various inflammatory immunological parameters related to immune-mediated arthritis having been determined. These parameters can be used to evaluate the efficacy of compounds in the CIA model (5). RA is preferably diagnosed after assessing the Disease Activity Score (DAS) index or the related DAS28 (6), including measurements of various parameters and symptoms in an individual. The assessment of said indices may be performed by a clinician examining an individual. In a more preferred embodiment, said medicine is capable of alleviating one or more symptom(s) of a treated patient and / or one or more characteristic(s) or parameter(s) of a cell, tissue or organ of a treated patient is / are improved using a source of L19 or a composition of the invention when said medicine is capable of inducing a significant change in the DAS or DAS28. Other ways of assessing rheumatoid arthritis are also described in (6) and in (7). A medicine, as defined in this document, is capable of improving a parameter if, after at least one week, one month, six months, one year or more of treatment using a source of L19 or a composition of the invention.Preferably, the value of said parameter has improved by at least 1%, 2%, 5%, 10% or more, compared to the value of said parameter before the start of treatment. A medicament, as defined in this document, is capable of alleviating a symptom or characteristic of a patient or of a cell, tissue, or organ of said patient if, after at least one week, one month, six months, one year or more of treatment using a source of LI 9 or a composition of the invention, said symptom or characteristic is no longer detectable. Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, including ulcerative colitis and Crohn's disease. Ulcerative colitis is characterized by inflammation of the colon, resulting in frequent bowel movements, diarrhea and associated spasms, fever, and weight loss. The lining of the colon becomes damaged, forming ulcers that release mucus, pus, and blood. Repeated episodes can lead to scar tissue formation and death of colon tissue, or sepsis in severe cases. Current treatments focus on suppressing the abnormal inflammatory process in the colon lining. A well-characterized animal model for human IBD, ulcerative colitis, and especially Crohn's disease is the 2,4,6-trinitrobenzenesulfonic acid / ethanol (TNBS)-induced colitis model. Colitis induced by intrarectal administration of TNBS. This induces a T-cell mediated immune response in the colonic mucosa, leading to massive mucosal inflammation, characterized by T-cell and macrophage infiltration throughout the large intestine wall. The histopathological nature is accompanied by progressive weight loss, bloody diarrhea, and thickening of the large intestine wall (8). Current animal models of colonic inflammation do not fully reflect the complexity of the disease in humans; however, they are valuable tools for evaluating the efficacy of therapeutic compounds. Psoriasis is a common chronic skin disease in which new skin cells grow abnormally, resulting in inflamed, swollen, and scaly patches of skin where old skin has not fallen off quickly enough. The most common form is plaque psoriasis, characterized by lesions covered with silvery-white scales. Psoriasis may be limited to a few lesions or may involve extensive areas of skin, most commonly appearing on the elbows, knees, scalp, and trunk. Mild cases of psoriasis are controlled by topical applications. However, more severe cases require ultraviolet radiation therapy, which is inconvenient, or the use of systemic immunosuppressive therapies that, due to toxic side effects, are often of limited value for long-term use. Furthermore, psoriasis frequently recurs, including soon after discontinuation of immunosuppressive therapy. Several disease models have been developed for the evaluation of potential disease modulators. One such model is an in vivo xenograft model for psoriasis with human psoriatic skin implanted in a severely immunodeficient (SCID) mouse. Therapies that abolish or reduce inflammation can be tested by administering human inflammatory tissue to SCID mice. Treatment efficacy can be assessed by a series of indices. Psoriasis is a disease that is preferably diagnosed after assessing the psoriasis area and severity index (PASI), clinical global assessment (PGA) (9) or NPF psoriasis score (NPF-PS), including measurements of various parameters and symptoms on an individual. The assessment of said indices can be performed by a clinician examining an individual.In a more preferred embodiment, said medicine is capable of relieving one or more symptom(s) of a treated patient and / or one or more characteristic(s) or parameter(s) of a cell, tissue or organ of the treated patient is / are improved using a source of E19 or a composition of the invention when said medicine is capable of inducing a significant change in PASI, PGA or NPF-PS. Other ways of assessing psoriasis include the Dermatology Life Quality Index (DLQI) (10) and the Salford Psoriasis Index (SPI), as described. defined ei ti (11) · A medicine, as defined in this document, is capable of improving a parameter if, after at least one week, one month, six months, one year or more of treatment using a source of L19 or a composition of the invention. Preferably, the value of said parameter has been improved by at least 1%, 2%, 5%, 10% or more, in from the beginning of said parameter of the comparison value before treatment A medicine, as defined in this document, capable of alleviating a symptom or characteristic of a patient or of a cell, tissue or organ of said patient if, after at least one week, one month, six months, one year of treatment or more using a source of L19 or a composition of the invention, said symptom or characteristic is no longer detectable. A preferred source of L19, as defined in this document, is for the prevention or treatment of an inflammatory disorder in an individual. An individual who may be treated using such a source of L19 may already have been diagnosed as having an inflammatory disorder. Alternatively, an individual who can be treated using such a source of L19 may not yet have been diagnosed as having an inflammatory disorder, but may be at higher risk of developing an inflammatory disorder in the future, given their genetic history. A preferred individual is a human being. Composition In another aspect, a composition is provided comprising a source of L19, as defined in this document. In a preferred embodiment, said composition is preferably a pharmaceutical composition, said pharmaceutical composition comprising a pharmaceutically acceptable vehicle, salt, diluent and / or excipient. Such pharmaceutical composition may comprise any pharmaceutically acceptable vehicle, filler, salt, preservative, solubilizer, diluent and / or excipient. Such pharmaceutically acceptable vehicle, filler, salt, preservative, solubilizer, diluent and / or excipient may, for example, be found in (12). Each characteristic of said composition has been previously defined in this document. If multiple L19 sources are used, the dose, as defined in this document, may refer to the total dose of all L19 sources used or the dose of each L19 source used or added. Therefore, in one embodiment, a composition is provided in which each total quantity of the L19 source used is dosed in an amount of 0.1 mg / kg and 100 mg / kg. The invention particularly favors the use of an excipient that will aid in the release of each of the components, as defined herein, to and / or within a cell. Preferred excipients are those capable of forming complexes, nanoparticles, micelles, vesicles, liposomes, proteoliposomes, and / or virus-like particles (VLPs) that deliver each constituent as defined herein, complexed or trapped within a vesicle or liposome across a cell membrane. Many of these excipients are known in the art. Suitable excipients comprise polyethyleneimine (PEI) or similar cationic polymers, including polypropyleneimine or polyethyleneimine copolymers (PECs) and derivatives, synthetic amphiphiles (SAINT-18) lipofectin™, DOTAP, and / or viral capsid proteins that are capable of self-assembling into particles that can release each constituent as defined herein to a cell. Depending on their identity, a person skilled in the art will know which type of formulation is most suitable for each constituent, as defined in this document. In a preferred embodiment, the invention provides a composition or preparation that is in the form of a parts kit comprising a source of L19, as defined in this document. A medicine, remedy, or pharmaceutical composition, as defined herein, may be administered locally or systemically. A medicine is preferably administered parenterally, for example, by intravenous, subcutaneous, intraperitoneal, intramuscular, intradermal, intra-arterial, or intralesional injection or infusion. A preferred mode of administration is subcutaneous or transdermal. An example of transdermal administration is a cream. The invention is not limited to a specific mode of administration of a medicine or a source of L19 or a composition, as defined herein. A preferred mode of administration is oral administration using a capsule or a tablet. Alternatively, a medicine, a source of L19, or a composition, as defined herein, may be administered locally via a catheter or pump, or by a suppository or cream.Alternatively, a medication, a source of L19, or a composition, as defined in this document, may be administered topically. The formulation of a medicament, a source of L19 or a composition, as defined in this document, depends on the intended mode of administration and application (therapeutic). A pharmaceutical vehicle may be any compatible non-toxic substance suitable for administering said compound to an individual. For example, sterile water, or solid vehicles, inerts or excipients may generally be supplemented with pharmaceutically acceptable agents such as buffering agents, dispersing agents and the like. Compositions will either be a liquid; for example, a stabilized suspension of said compound, or a composition comprising said compound, or will have solid and / or dry forms: for example, powder. For oral and rectal administration, the said compound may be administered in solid dosage forms, such as capsules, tablets, suppositories and powders, or in liquid dosage forms, such as elixirs, syrups, creams, ointments and suspensions. Another form may be a semi-solid or semi-liquid form, in which the said compound is present as a liquid form in or on a solid support, such as a plaster. A composition can be in liquid, solid, semi-liquid, or semi-solid form, as already defined in this document. In a preferred embodiment, other compounds are used sequentially or simultaneously with a source of or a composition in order to improve specificity. L19 of prophylactic or therapeutic treatment. It is advantageous, for example, to use other compounds that will further enhance the anti-inflammatory response of the treated individual. More preferably, such compounds are not present in a single composition together with a source of L19 or composition. Such a compound may be an antibody, a DMARD (disease-modifying antirheumatic drugs), NSAIDs (non-steroidal anti-inflammatory agents) and / or an IL-10 inducer, such as those described in Table 1 of (13).An IL-10 inducer includes a compound selected from the group consisting of: cordycepin, a gold salt, a corticosteroid, cyclosporine A, ST1959 3-(2-ethylphenyl)-5(3-methoxyphenyl)-1H-1,2,4-triazole, SR 31747A, SSR 125329A, aprotinin), linomide, monomethyl fumarate, agents that increase cAMP levels, such as rolipram or cicaprost, a catecholamine, vitamin D3, a fish oil comprising the n-3-polyunsaturated fatty acid, the sex hormone estriol, KM 2210 or bestrabucil, type I IFN, such as IFN-τ, IFN-β or IFN-β, autoantigen mimics such as glatiramer acetate (copolymer pI), a pyrimidinylpiperazine or a derivative of same, 1-ethyl-3-(3-dimethylamhopropyl)urea dihydrochloride, 5'-methylthioadenosine and a pirfenidone such as 5-methyl-1-phenyl-1H-pyridinone. Use In another aspect, the use of a source is provided. L19 or a composition, as defined in this document, for the manufacture of a medicament for the prevention or treatment of an inflammatory disorder in an individual. Each characteristic of said use has already been defined in this document. A treatment in a use or method according to the invention is at least one week, at least one month, at least several months, at least one year, at least 2, 3, 4, 5, 6 years or more. Each source of L19, as defined in this document, for use in accordance with the invention, may be suitable for direct administration in vivo, in vitro or ex vivo to a cell, tissue and / or organ of individuals affected by or at risk of developing an inflammatory disorder, and may be administered directly in vivo to said individuals. The frequency of administration of an L19 source or composition of the invention may depend on several parameters, such as the patient's age, the number of molecules (i.e., dose), and the formulation of said molecule. The frequency can be daily, weekly, or vary between at least once every two weeks, three weeks, four weeks, or five weeks, or over a longer period of time. Method In another aspect, a method is provided for relieving one or more symptoms of an inflammatory disorder in an individual, or in a cell, tissue or organ of said individual, or relieving one or more characteristic(s) or symptoms of an individual or a cell, tissue or organ of said individual, the method comprising administering to said individual a source of L19 or a composition, as defined herein. In one embodiment, the said method is performed in vitro, for example, using a cell culture or a tissue culture. The said method may also be ex vivo. i Preferably, said method is in vivo. Each characteristic of these methods has already been defined in this document. In one method of the invention, a source of LI9 can be combined with an additional compound known to be used in the treatment of an inflammatory disorder in an individual. Such a compound may be an antibody, a DMARD (disease-modifying antirheumatic drugs), an NSAID (non-steroidal anti-inflammatory drugs) and / or an IL-10 inducer, as described in (13). Preferred IL-10 inducers have already been identified earlier in this document. Definitions Nucleic acid molecule A nucleic acid molecule can be either cDNA or synthetic DNA. DNA can be double-stranded or single-stranded, and if single-stranded, it can be coding or non-coding (antisense) strand. DNA or RNA with a structure modified for stability or other reasons is additionally part of the invention. A nucleic acid molecule is represented by a nucleotide sequence. A nucleotide sequence can be an allelic variant of the nucleotide sequence according to the invention. If desired, the nucleotide sequence can be prepared or synthetically altered so that known codon preferences of the intended expression host can be advantageously used. Depending on the size of the nucleic acid molecule, it could be identified as an oligonucleotide. An oligonucleotide can comprise at least 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100 nucleotides. Polypeptide Polypeptide, as used in this document, refers to any peptide, oligopeptide, polypeptide, gene product, expression product, or protein. A polypeptide is represented by a sequence of amino acids. It may comprise from 2 to 267 (i.e., the length of SEQ ID No: 1, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, or 29) or from 5 to 265, from 8 to 260, or from 10 to 250 amino acids. It may comprise more than 267 amino acids. The term polypeptide encompasses naturally occurring or synthetically occurring molecules. An oligopeptide may comprise from 2 to 20 amino acids. A peptide may comprise from 5 to 10, from 5 to 20, from 5 to 30, or from 5 to 50 amino acids. Identity / similarity Sequence identity is defined in this document as a relationship between two or more amino acid sequences (polypeptide, protein, peptide, or protein fragment) or two or more nucleic acid sequences (polynucleotide, nucleic acid, nucleotide, or oligonucleotide), as determined by comparing the sequences. In a preferred embodiment, sequence identity is calculated based on the entire length of two given SEQ ID NOs or on parts thereof. Part of the same preferably means at least 50%, 60%, 70%, 80%, 90% or 10% of both SEQ ID NO. In the technique, identity also means the degree of sequence relationship between the amino acid or nucleic acid sequences, as the case may be, and is determined by the pairing between the strands of such sequences. Similarity between two amino acid sequences is determined by comparing the amino acid sequence and its conserved amino acid substitutes of one polypeptide with the sequence of a second polypeptide. Identity similarity can be easily calculated by known methods, including, but not limited to, those described in (Computational Molecular Biology, Lesk, AM, ed., Oxford University Press, New York, 1988; Biocomputing: Informatics and Genome Projects, Smith, DW, ed., Academic Press, New York, 1993; Computer Analysis of Sequence Data, Part I, Griffin, AM, and Griffin, HG, eds., Humana Press, New Jersey, 1994; Sequence Analysis in Molecular Biology, von Heine, G., Academic Press, 1987; and Sequence Analysis Primer, Gribskov, M. and Devereux, J., eds., M Stockton I Press, New York, 1991; and Carillo, H., and Lipman, D., SIAM J. Applied Math., 48: 1073 (1988). Preferred methods for determining identity are designed to provide the highest possible match between the tested sequences. Methods for determining identity and similarity are encoded in publicly available computer programs. Preferred computer program methods for determining identity and similarity between two sequences include, for example, the program package... GCG (Devereux, J., et al., Nucleic Acids Research 12 (1): 387 (1984)), BestFit, BLASTP, BLASTN and FASTA (Altschul, SF et al., J. Mol. Biol. 215:403-410 (1990). The BLAST Altschul, S., et al., NCBI NLM NIH Bethesda, MD 20894; Altschul, S., et al., J. Mol. Biol. 215:403-410 (1990). The well-known Smith-Waterman algorithm can also be used to determine identity. Preferred parameters for polypeptide sequence comparison include the following: Algorithm: Needleman and Wunsch, J. Mol. Biol. 48:443-453 (1970); Comparison matrix: BLOSSUM62, by Hentikoff and Hentikoff, Proc. Natl. Acad. Sci. USA. 89:10915-10919 (1992); Gap Penalty: 12; and Penalty for Gap Extension: 4. A useful program with these parameters is publicly available as the □gap program from Genetics Computer Group, located in Madison, TfL. The above-mentioned parameters are the predefined parameters for amino acid comparisons (juntamenti = with no penalty for end gaps 2). Preferred parameters for nucleic acid comparison include the following: Algorithm: Needleman and Wunsch, J. Mol. Biol. 48:443-453 (1970); Comparison matrix: Matches = +10, Non-matches = 0; Interval Penalty: 50; Interval Length Penalty: 3 Available as the Gap program from Genetics Computer Group, located in Madison, Wis. The above are the predefined parameters for nucleic acid comparisons. Optionally, in determining the degree of amino acid similarity, a person skilled in the art may also take into consideration so-called conservative amino acid substitutions, as will be evident to a person skilled in the art. Conservative amino acid substitutions refer to the interchangeability of residues with similar side chains. For example, a group of amino acids with aliphatic side chains comprises glycine, alanine, valine, leucine, and isoleucine; a group of amino acids with aliphatic hydroxyl side chains comprises serine and threonine; a group of amino acids with amide-containing side chains comprises asparagine and glutamine; a group of amino acids with aromatic side chains comprises phenylalanine, tyrosine, and tryptophan; A group of amino acids with basic side chains is formed by lysine, arginine, and histidine; and a group of amino acids with sulfur-containing side chains is cysteine, i.e., methionine. Preferred conservative amino acid substitution groups II are: valine-leucine-isoleucine, phenylalanine-tyrosine, lysine-arginine, alanine-valine, and asparagine-glutamine. Substitution variants of the amino acid sequence disclosed in this document are those in which at least one residue in the disclosed sequences has been removed and a different residue has been inserted in its place. Preferably, amino acid substitutions are conservative. Preferred conservative substitutions for each of the naturally occurring amino acids are as follows: Ala for ser; Arg for lys; Asn for gin or his; Asp for glu; Cys for ser or ala; Gin for asn; Glu for asp; Gly for pro; His for asn or gln; Ile for leu or vai; Leu for ile or vai; Lys for arg; gin or glu; Met for leu or ile; Phe for met, leu or tyr; Ser for thr; Thr for ser; Trp for tyr; Tyr for trp or phe; and, Vai for ile or leu. i : I : Hybridization conditions The hybridization conditions for a Modern nucleic acid molecule to have low, medium, or high stringency (Southern blotting procedures). Low, medium, or high stringency conditions mean pre-hybridization and hybridization at 42 °C in 5x SSPE, 0.3% SDS, i: 200 pg / mL eg of denatured and cut salmon sperm DNA and 25%, 35%, or 50% formamide for low, medium, or high stringency, respectively. Subsequently, the hybridization reaction is washed three times for 30 minutes each, using 2x SSC, 0.2% SDS, and 55°C, 65°C, or 75°C for low, medium, or high stringency, respectively. Nucleic acid construct / expression / control sequences A nucleic acid construct comprises a A nucleotide sequence that codes for a protein or a protein fragment, as defined in this document. A nucleic acid construct comprising a nucleic acid molecule that codes for a particular protein or The protein fragment, as defined in this document, will ensure the expression of the given nucleic acid molecule. and the corresponding protein or protein fragment in a treated individual. In a more preferred embodiment, a nucleic acid construct comprises more than one nucleic acid molecule, each nucleic acid molecule encoding a given protein or protein fragment. In a still more preferred embodiment, a nucleic acid construct comprises two, three, or four nucleic acid molecules, each nucleic acid molecule encoding a given protein or protein fragment. protein. In a preferred embodiment, a nucleic acid construct© comprises an expression cassette, said expression cassette comprising each required nucleic acid molecule. Each nucleic acid molecule is operably linked with another nucleic acid molecule. present. More preferably, a suitable promoter is operably linked with the expression cassette to ensure the expression of the nucleic acid molecule in an individual. Operably linked is defined in this document as a configuration in which a control sequence is suitably placed at a position relative to the nucleotide sequence encoding the polypeptide of the invention, such that the control sequence directs the production / expression of the polypeptide of the invention in a cell and / or in an individual. It will be understood that expression includes any step I involved in the production of the polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion. A sequence, including advantageous sequences, is defined in this document as all the components that are necessary for the expression of a polypeptide. At a minimum, control sequences include a promoter and transcription and translation signals. Optionally, a promoter represented by a nucleotide sequence present in a nucleic acid construct is operably linked to another nucleotide sequence that encodes a nucleic acid molecule, as identified in this document. i An expression vector can be any vector that can be conveniently subjected to recombinant DNA processes and that can cause the expression of a nucleotide sequence encoding a polypeptide of the invention in a cell and / or in an individual.As used in this document, the term promoter refers to a nucleic acid fragment that functions to control the transcription of one or more genes or nucleic acids, located upstream with respect to the transcription direction of the gene's transcription initiation site, and is related to the binding site identified by the presence of a binding site for DNA-dependent RNA polymerase, transcription initiation sites, and any other DNA sequences including, but not limited to, transcription factor binding sites, activator and repressor protein binding sites, and any other nucleotide sequences known to a person skilled in the art to act directly or indirectly to regulate the amount of transcription from the promoter. [Within the context of the invention, a J promoter preferably terminates at nucleotide -1 of the transcription start site (TSS).] Unless otherwise indicated, each modality, as described in this document, may be combined with another modality, as described in this document. In this document and its claims, the verb "to comprise" and its conjugations are used in their non-limiting sense to mean that the items written after the word are included, but items not specifically mentioned are not excluded. Furthermore, the verb "to consist" can be replaced by "to consist essentially in," meaning that a source of L19 or a composition, as defined in this document, may comprise additional component(s) to those specifically identified, said additional component(s) not altering the unique character of the invention. Furthermore, referring to an element with the indefinite article "a" or "an" does not exclude the possibility that more than one of the elements is present, unless the context clearly requires that there is one and only one of the elements; the indefinite article "a" or "an," therefore, generally means at least one. The word approximately or about, when used in association with a numerical value (approximately 10, about 10), preferably means that the value may be the given value of 10 plus or minus 1% of the value. All patents and literature references cited in this descriptive report are hereby incorporated by reference in their entirety. Each embodiment, as identified herein, may be combined with another, unless otherwise indicated. The invention is further explained in the following examples. These examples do not limit the scope of the invention, but only serve to explain the invention. Brief Description of the Drawings Figure 1. Purification of his-LmL19. SDS-PAGE gel, showing the different steps in the purification of the rLmL19 protein. (1) Standard molecular weight. Total bacterial extracts after (2) and before passage through the column (3). (4) Purified protein. Figure 2. Production of IFN-gamma and IL-10 by j splenocytes from naive BALB / c mice (n=6) stimulated in vitro with LmL19. The (P-value obtained after statistical analysis using Student's t-test is shown. Differences in cytokine production between cells stimulated with LmL19 or Concanavalin I (ConA) were considered significant when P<0.05*). Figure 3. Production of IFN-gamma and IL-10 by PBMCa from healthy human donors (n=3) stimulated in vitro with LmL19. The (P-value obtained after statistical analysis using Student's t-test is shown. Differences in cytokine production between cells stimulated with LmL19 or ConA were considered significant when P<0.05*). Figure 4. Schematic representation of the recombinant protein MBP-LmL19. Figure 5. TNF concentration in the different study groups after 24 hours of incubation (pg / mL). Values ​​are presented as mean ± standard deviation. #; P<0.005, test groups without irradiation compared to the control group.*; P<0.005, irradiated test groups compared to the control / UV group. Figure 6. IL-10 concentration in the different study groups after 24 hours of incubation (pg / mL). Values ​​are presented as mean + standard deviation.#; P<0.005, test groups without irradiation compared to the control group.*; P<0.005, irradiated test groups compared to the control / UV group. Figure 7. Production of the LmL19 peptide from 11-10. Cells were obtained and cultured as indicated in the text. IL-10 levels in culture supernatants were analyzed by ELISA. The assay was performed once using pooled cells obtained from three naive mice (analyzed in duplicate) * P<0.05 when each group was compared with j unstimulated cells. Examples Example 1 Cloning and expression. The gene was characterized after an in silico search in the L. major genome database. Based on the sequence, two oligonucleotides were synthesized (see below) and used as primers for a PCR using DNA extracted from L. major parasites [clone VI (MHOM / IL / 80 (Friedlin)]]. The obtained DNA was digested with BamHI / HindIII, cloned into the corresponding sites of the pBluescript plasmid, and sequenced. The obtained DNA sequence and the deduced amino acid sequence are shown below, respectively. i : A. Oligonucleotides used, ί LmL19D: cgGGATCCATGACCCCTCTCTCCCTCTC (SEQ ID NO:3) (underlined, a BamHI cutting site was included for cloning purposes). í LmL19R: cccAAGCTTTTACTTCTTCGACTTCTTCAC (SEQ ID NO: 4) (underlined, a HindIII cutting site was included for cloning purposes). B. Nucleotide sequence. (The restriction enzyme cleavage sites are included and marked in italics and underlined: these sites do not belong to the nucleic acid molecule that encodes L19 of Leishmania major or Lm) LmL19 sequence analysis (SEQ ID NO: 2 is the sequence (below without the added underlined sequence for cloning purposes) GGATCCATGA CCCCTCTCTC CCTCTCTTCC TCCCGCCACA GTTTTAAGCA GAACGAAACG CAGAACATGG TGTCTCTGAA GCTGCAGGCT CGCCTTGCGT CGAGCATCCT CGGCTGCGGC CGCGCGCGCG TGTGGCTGGA CCCCAACGAG GCGGTGGAGA TCCAGAACGC GAACTCGCGC AAGAGCGTGC GCAAGCTGAT CAAGGATGGC TTCATCATCC GCAAGCCGGT GAAGGTGCAC TCGCGCGCGC GGTGGCGTAA AATGAAGGAG GCGAAGGACA TGGGGCGCCA CAACGGCGTT GGGCGCCGCG AGGGTAGCCG CGAGGCCCGC ATGCCGAGCA AGGAGTTGTG GATGCGCCGC CTGCGCATTC TGCGCCGCCT GCTGCGCAAG TACCGCGCGG ACAAGAAGAT TGACCGCCAC GTGTAGCGCG ACCTGTACAT GCGCGCGAAG GGTAACGTGT TCCGCAACAA GCGCAACCTT GTGGAGCACA TCCACAAGAT CAAGAATGAG AAGAAGAAGG AGCGCCAGCT GGCGGAGCAG CTCGCGGCGA AGCACCTGCG CGACGAGCAG AACCGCCAACA AGGCTCGCAA GCAGGAGCTG AAGAAGCGCG AGAAGGAGCGG CGAGCGCGCG AGGCGCGACG ACGCTGCTGC CGCTGCGCAG AAGAAGAAGG CGGACGCCGC GAAGAAGTCC GCCGCGCCTG CTGCGAAGTC CGCCGCGCCT GCCGCGAAGG CTGCTGCCCC CGCCACGAAG GCCGCTGCTG CTGCCCCCGC CACGAAGGGT GCTGCGCCGG TGAAGAAGTC GAAGAAGTAA AAGCTT C. Sequência de aminoãcidos deduzida (SEQ NO ID: 1) MTPLSÍSSSR HSFKQNETQN MVSLKLQARL ASSILGCGRA RVWLDPNEAV EIQNANSRKS VRKLIKDGFI IRKPVKVHSR ARWRKMKEAK DMGRHNGVGR REGSREARMP SKELWMRRLR ILRRLLRKYR ADKKIDRHVY RDLYMRAKGN VFRNKRNLVE HIHKIKNEKK KERQLAEQLA AKHLRDEQNR NKARKQELKK REKERERARR DDAAAAAQKK KADAAKKSAA PAAKSAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA The DNA encoding LmL19 was subcloned into the BamHI / HindIII sites of the prokaryotic expression plasmid pQE-30, allowing the production of the recombinant protein fused to Gxhistidines. Escherichia coli (M15 strain) cultures transformed with the recombinant plasmid were used for the expression of the recombinant protein. Initial assays were performed at 37°C, but it was observed that the protein degraded within the bacteria. For this reason, the cultures were induced at 30°C in order to decrease protein degradation. Under these conditions, we observed a low production of the intact recombinant protein. Thus, rLmL19 was purified by affinity chromatography under denaturation conditions. The purified protein obtained shows some degradation bands with lower molecular weight (Figure 1). The recombinant proteins were passed through a polymyxin-agarose column to remove endotoxins. Stimulation of mouse spleen cells with recombinant rLmL19. Single-cell preparations of spleen tissue were plated in duplicate in 24-well plates at 5 x 10⁶ cells / mL. The cells were incubated in complete RPMI medium supplemented with 2 mM L-glutamine, penicillin (100 U / mL), i; Streptomypin (100 pg / mL) and inactivated fetal bovine serum I: The spleen cells were induced by heat treatment at 10% alone (basal control; medium) or stimulated with rLmL19 (12 µg / mL) or ConA (1 µg / mL) at 37°C in 5% CO2 for 72 h. The release of IFN-γ and IL-10 in the culture supernatants was evaluated by sandwich ELISA (Figure 2). It can be concluded that the recombinant protein LmL19 induced a specific production of IL-10 without the production of IFN-γ by spleen cells obtained from naive mice. Stimulation of human peripheral blood mononuclear cells (PBMCs) with recombinant rLmL19. PBMCs were obtained from heparinized venous blood by passing it through a Ficoll-Hypaque gradient. PBMCs were washed. three times and resuspended at a concentration of 5 x 10⁶ cells / mL in RPMI supplemented with 2 mM L-glutamine, penicillin (100 U / mL), streptomycin (100 pg / mL) (Gibco, NY) and 10% heat-inactivated human AB serum. The cells Cells were plated onto 24-well tissue culture plates at a concentration of 5 x 10⁶ cells / mL and incubated at 37°C, 5% CO₂. Stimulation was performed by adding rLmL19 (20 pg / mL and 5 pg / mL) and ConA (1 pg / mL) for 72 h. As above, the release of IFN-γ and IL-10 in the culture supernatants was evaluated by sandwich ELISA (Figure 3). As with mouse spleen cells, PBMCs from healthy human donors produced IL-10 after in vitro stimulation with recombinant LmL19. The production of this cytobin was dose-dependent. Expression of rLmL19 as a fusion protein with maltose-binding protein. These preliminary results indicated that the rLmL19 protein was able to induce the release of IL-10 from human and mouse leukocytes. The production level of the recombinant protein was not yet optimal. In order to improve protein production, the DNA encoding the LmL9 protein was cloned into the prokaryotic expression vector pMal-c2. This vector allows the production of heterologous proteins in E. coli fused with the bacterial protein MBP. As shown in Figure 4, the fusion protein and the heterologous protein can be separated using a specific protease (factor Xa) due to the presence of a factor Xa cleavage site between the two proteins. i The transformed E. coli (XLl-blue strain) cultures! Recombinant plasmids were used for recombinant protein expression. The protein was overexpressed as a soluble product that was purified by affinity chromatography under native conditions on amylose columns. Using this system, a higher level of recombinant protein was obtained (not shown). Example 2: skin study The aim of this study was to evaluate the anti-inflammatory capacity of a protein called L19 in human skin explants. This was done using an analytical method to study the protective efficacy of this protein against ultraviolet (UV) light radiation in the skin. The basis of this work is the performance of a single inflammatory study on skin explants to evaluate the anti-inflammatory capacity of said product versus light radiation. UV. The study was divided into the following tasks to achieve the proposed objective. Basic cytotoxicity analysis A single assay was performed using the MTT technique to determine the maximum concentration of the product to be analyzed in the efficacy analysis. This is a colorimetric assay based on the metabolic reduction of tetrazolium salts (MTT) due to the cellular metabolism (cellular respiration) of mouse fibroblasts (BALB / 3T3). This metabolic reduction of MTT is caused by the mitochondrial enzyme succinate (formazane), which produces a blue compound that determines the mitochondrial functionality of the treated cells. The number of live cells is proportional to the resulting blue color. The product was incubated at 8 different concentrations (6 replicates of each concentration) for 24 hours. Analysis of anti-inflammatory efficacy: Efficacy was evaluated by an anti-inflammatory study consisting of a single assay on skin explants that analyzed two interleukins present in inflammation caused by UV radiation, using the technique of... ELISA. The study groups were as follows: • Healthy control group. 3 skin explants. These did not receive UV light radiation. • Damaged group. 3 skin explants irradiated with UV light. Test group. 9 skin explants irradiated with UV light and then incubated with recombinant Lm LI9 (SEQ NO ID:1) expressed in E. coli. • Test group 2. 9 non-irradiated skin explants were then incubated with Lm Ll9 (SEQ ID NO:1) expressed in E. coli. Three different product concentrations, 3 replicates per concentration (the highest product concentration was determined by product toxicity analysis). After irradiation of the explants with ultraviolet light, Lm L19 (i.e., SEQ ID No: 1) expressed in E. coli was incubated; 24 hours later, two interleukins involved in the inflammatory effect caused by ultraviolet light on skin were measured, IL-10 and TNFα. MATERIALS AND METHODS cell cultures As the experimental system for cytotoxicity analysis, the study used a cell culture of immortalized mouse fibroblasts from the BALB / 3T3 cell line of the European Collection of Cell Cultures (ECACC), Cat. No. 86110401. Immortalized ECACC fibroblasts were grown in DMEM medium with 10% FCS (fetal calf serum). After thawing, the cells were cultured in a monolayer in a humid atmosphere with 5% CO2 at a temperature of 37°C. During this time, the culture medium was changed every 2 to 3 days, according to the supplier's instructions. After this period, when the culture flasks reached 80% confluence, the cells were distributed into 96-well plates, with a concentration of 5,000 cells per well. MTT cytotoxicity study During the cytotoxicity assay, cells were treated with different concentrations of the study product known as L19. After 24 hours of treatment, MTT staining was performed. This assay is based on the metabolic reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol bromide (MTT) or tetrazolium salts (yellow and soluble) produced by the mitochondrial enzyme succinate dehydrogenase, which generates a blue-colored compound (formazane) that allows the determination of mitochondrial functionality in treated cells. This method is widely used to measure cell proliferation and survival. The number of live cells is proportional to the amount of formazane produced. Since dead cells do not respire, they do not have the enzyme and therefore cannot reduce it, as they lack succinate dehydrogenase. The greater the reduction in MTT concentration, the bluer the color and the greater the cell viability. The experiment was performed in 96-well plates with 3T3 cells cultured in a monolayer with confluence of 80%. These cytotoxicity studies allowed us to determine LC80, LC50, and LC20 values ​​(concentrations of the product that reduce cell viability by 80%, 50%, and 20%, respectively). During this task, a plate of immortalized fibroblasts was incubated with eight distinct concentrations of L19 protein for 24 hours (1 product plate with 6 replicates per concentration analyzed) and a second MTT assay control plate with sodium dodecyl sulfate (SDS) at eight distinct concentrations (1 MTT plate, with 6 replicates per concentration analyzed) served as the toxicity reference product. This was used to establish a standard curve for cell death. All study plates were also seeded with fibroblasts in at least 12 wells that were used as healthy controls, and 3T3 cultures with only the culture medium, where L19 was not added to the study plate nor SDS to the cell death control plate (SDS data: LQ20: 0.124 mg / mL; LC50: 0.142 mg / mL; LC80: 0.163 mg / mL). According to good the concentration of L19 protein provided by LETI, the highest concentration analyzed was 200 pg / mL in dilutions. 1:2. The final concentrations used are detailed below: C2: C3: C4: C5:C6:C8:1.56 pg / ml. After incubation, the plates were developed with MTT and the absorbance was measured at 540 nm with an ELISA plate reader. The results obtained were used to calculate the lethal concentration values ​​LC80, LC50, and LC20 in fibroblast cultures for the products under study. Interleukin-10 and TNFα determination assay The quantification assay for interleukin-10 and TNFα was performed using the supernatant from skin explant culture media. Quantitative determination of IL-10 and TNFα was performed using BD OptEIA™ ELISA kits manufactured by Becton Drive, Franklin Lakes, NJ, USA: ELISA Kit II. Human TNF The efficacy of L19 was evaluated by quantifying UV radiation-induced interleukins in human skin explants. ii Exposure to light from the solar simulator: The plate containing the skin samples was exposed to UV / Vis light emitted by a SOL 500 solar simulator (Dr. Hônle). The light intensity was measured throughout the exposure process using a UV light meter. Radiation doses can be adjusted using these values, considering that during 5 minutes of exposure, the cells receive approximately 1 J / cm² at that intensity. The final exposure time for the skin explants was 50 minutes, implying a radiation of 10 J / cm². The groups included in the study were: • Healthy control group. 3 skin explants. ii These did not receive UV light radiation. • Group of damage. 3 explants of skin irradiated with UV light. • Test group. 9 skin explants irradiated with UV light and then incubated with recombinant Lm LI9 (i.e., SEQ ID No:l) expressed in E. coli. • Test group 2. 9 non-irradiated skin explants were then incubated with Lm L19 (i.e., SEQ ID NO:1). | Three different product concentrations, 3 replicates per concentration (the highest product concentration was determined by product toxicity analysis). After irradiation of the explants with ultraviolet light (10 J / cm2), they were incubated with product L19. After 24 hours, two interleukins involved in the inflammatory effect caused by ultraviolet light on the skin were measured: IL-10 and TNFα. IL-10 and TNFα were quantified by adding 100 pL of each of the IL-10 and TNFα standards included in the kits manufactured by BD Biosciences (BD OptEIA™ ELISA Kits: IL-10, Cat. No. 555157 and TNFα, Cat. No. 555212), as well as 100 pL of the culture medium used to incubate each sample, all in duplicate and incubating in ELISA plates at room temperature for 2 hours. The wells were then washed with PBS, 200 pL of the conjugate solution was added, and incubation was carried out for 1 hour. The wells were then washed again, 200 pL of the substrate solution was added, and incubation was carried out for 20 minutes at room temperature. Finally, 50 pL of the stopping solution was added and the absorbance was read at 450 nm, with a reference of 540 nm. The absorbance results were extrapolated to the amount of IL-10 and TN Fa, using the curve obtained with the standards of both cytokines as a reference. RESULTS AND DISCUSSION Basic cytotoxicity analysis Cytotoxicity study of the L19 protein. To determine the maximum concentration of the product in the efficacy analysis study, a single assay was performed using the MTT technique on an immortalized fibroblast cell line, BALB / 3T3, which were seeded in 96-well plates, with an approximate density of 5,000 cells per well. The product was incubated at 8 different concentrations (6 replicates of each concentration) for 24 hours. The results of this assay were used to define the concentrations needed to determine the LCeo, LCso, and LC20. LC is the lethal concentration of the substance. LCeo is the concentration of the substance at which 80% of the cell population dies, LC5o is the concentration of the substance at which 50% of the cell population dies, and LC20 is the toxic concentration of the substance at which 20% of the cell culture population dies. In these assays, each fibroblast plaque was incubated with six distinct active concentrations for 24 hours: C2: C3: C4: C5: C6: C8: 1.56 pg / mL. After incubation, the plates were prepared for MTT analysis and absorbance was measured at 540 nm with an ELISA plate reader. The following table shows LC80, LC50 and LC2 0, obtained for each product (Table 1), without statistical significance: Table 1. Results for LC20, LC50, and LC80 of protein. L19 of LETÍ obtained by cytotoxicity assays, MTT. 485,83934 228,357 22,03021 Values ​​are expressed as average (pg / mL). You The results obtained from this cytotoxicity assay took into account the absorbance values ​​in healthy control cultures that were not incubated with the product. As well as L19, as a reference of 100% of the cell death values, viability was 0% with the SDS product at a concentration > 175 pg / mL (SDS data: LC20: 0.124 mg / mL; LC50: 0.142 mg / mL; LC80: 0.163 mg / mL. Based on the results obtained in the cytotoxicity assay, it was decided that, for the next task, the analysis of the anti-inflammatory efficacy of the L19 protein, the highest concentration for testing the product would be 25 pg / mL, as well as 12.5 pg / mL and 6.25 pg / mL. The choice of the highest concentration, pg / mL, refers to the LC20. This value is suitable for testing the product on the skin, as it is at the minimum toxicity limit for the product. It should also be noted that the toxicity analysis was performed on a single fibroblast culture. Monocultures are always more sensitive to product toxicity than an organotypic culture, such as a skin exfoliate. Analysis of anti-inflammatory efficacy Study on the anti-inflammatory capacity of the L19 protein after UV light irradiation on human skin explants. Treatment of human skin explants with L19 protein (25 pg / mL, 12.5 and 6.25 pg / mL for 24 hours) (Lm L19 or SEQ ID No: 1) was performed to study the anti-inflammatory effect of the protein. The study groups were divided into explants that were irradiated with UV light and then incubated with L19 protein, and explants that were exposed to the product but not irradiated with UV light. The study was conducted on organotypic cultures of human skin explants from cosmetic surgery. The assay used two control groups: a culture without L19 protein or solar radiation, and a damage control group, a culture without the protein but irradiated with sunlight. The concentrations and conditions can be found below: • Control group: Skin explants under normal culture conditions. • Group LI9 - 25 pg / mL; Skin explants incubated with 25 pg / mL of protein for 24 hours. • Group L19 - 12.5 pg / mL; Skin explants incubated with 12.5 pg / mL of protein for 24 hours. · drupo LI9 - 6.25 pg / mL; Skin explants incubated with 6.25 pg / mL of protein for 24 hours. • Control / UV Group: Skin explants under normal culture conditions and irradiated with UV light, 10 J / cm2. • Group LI9 - 25 pg / mL / UV; Skin explants irradiated with UV light (10 J / cm2) and then incubated with 25 pg / mL of protein for 24 hours. • Group L19 - 12.5 pg / mL / UV; Skin explants irradiated with UV light (10 J / cm2) and then incubated with 12.5 pg / mL of protein for 24 hours. • Group L19 - 6.25 pg / mL / UV; Skin explants irradiated with UV light (10 J / cm2) and then incubated with 6.25 pg / mL of protein for 24 hours. At the end of the incubation period (24 hours), quantification was performed for both cytokines, IL-10 and 0 TNFoí, using the ELISA technique, to determine the quantity of these cytokines. A single assay was performed for this task, where the L19 protein from the LETI laboratories was analyzed. This assay used 3 replicates of each condition, and each replicate was analyzed by the ELISA technique in duplicate. The concentration of TNFa (Figure 5) and the concentration of IL-10 (Figure 6) for these study groups is shown below, both for skin explants irradiated with UV light and for those that were not irradiated. Figure 5 shows TNFα production in the skin explants under the conditions to which they were subjected. The inflammatory reaction produced by UV radiation in the Control / UV group (153.9 + 44 pg / mL) is significantly greater than in the control group without radiation (22.9 + 7.3 pg / mL). This indicates that radiation with 10 J / cm² of UV light (in monoculture, the radiation used is normally 1 J / cm²) in skin explants triggers an inflammatory reaction in this case. This reaction is sufficient to see if the L19 protein has anti-inflammatory effects after incubation in skin samples exposed to this level of radiation. As shown in the graph, the statistical study of this protein shows that TNFα production after UV light irradiation decreases significantly in explants that were subsequently incubated (for 24 hours) with L19 protein at concentrations of 25 and 12.5 pg / mL (23.3 ± 2.8 and 25.9 ± 4.8 pg / mL, respectively). The L19 - 6.25 pg / mL / UV group showed a non-significant reduction in the production of said cytokine. On the other hand, the graph also shows a significant increase in TNFα production in the L19 - 25 pg / mL, L19 - 12.5 pg / mL, and L19 - 6.25 pg / mL groups (which were not irradiated) compared to the control group. All of this leads us to consider that the L19 protein could affect the skin in some way, generating an inflammatory reaction. This last point should be corroborated by other studies. The significant decrease in TNFα production in the L19 protein cultures subsequently treated with solar radiation versus the Control / UV group leads us to consider that this protein may have an anti-inflammatory effect. Figure 6 shows the IL-10 production in skin explants under the conditions to which they were subjected. The IL-10 analysis in both irradiated and non-irradiated groups, incubated with L19 protein, indicated a significant increase in IL-10 production at all protein concentrations studied compared to the non-irradiated control group (p<0.005). In the statistical study, this increase was observed to a lesser degree compared to the control group irradiated with UV light, where only the L19 - 12.5 pg / mL / UV group showed a significant increase (*; p<0.005), 363.7 ± 22 pg / mL, versus the Control / UV group (203.1 ± 77). This is due to the standard deviations in the other two study groups, L19 - 6.25 pg / mL / UV and L19 - 25 pg / mL / UV (366 ± 94 and 724.8 ± 288 pg / mL), which causes the statistical study to determine differences greater than a statistical significance of 0.005. An increase in the number of replicates would improve the statistical significance. The data obtained indicate an increase in the production of IL-10, an anti-inflammatory biotin, which corroborates the results obtained for TNFα, leading to the possibility that the L19 protein triggers an anti-inflammatory cascade in skin explants, with an increase in IL-10 production. CONCLUSIONS In the cytotoxicity study, the toxicity of L19 protein was very low, at values ​​of 25 pg / mL. The choice of 25, 12.5, and 6.25 pg / mL to perform task 2 was based on cytotoxicity analysis. UV light radiation at 10 J / cm2 produces a significant inflammatory effect on skin explant samples not incubated with L19 protein and significantly increases TNFα and IL-10 levels (intrinsic anti-inflammatory reaction in the skin). Protein L19 causes a detectable reduction in the production of TNFα cytokines in skin samples irradiated with UV light. The L19 protein produces an overall increase in IL-10 levels in all groups incubated with the protein, both in samples subjected to UV light radiation and those not subjected to it. According to the results obtained, the ability of the L19 protein to activate an anti-inflammatory effect is very high. Example 3: IL-10-mediated production of LmL19 and LmL19-derived peptides Study objective To determine which regions of L19 (linear epitopes) are capable of inducing the production of 11-10 in spleen cultures. Material Twenty-four different peptides were designed and chemically synthesized. Each corresponds to a linear region of the L19 protein of Leishmania major (i.e., SEQ ID No:1). Each peptide comprises 20 amino acids derived from L19 of Leishmania major (i.e., SEQ ID No:1), except for peptide 24, which comprises only 14 amino acids. Each peptide overlaps with the previous peptide by 9 amino acids. 1: Peptide 1: MTPLSLSSSSRHSFKQNETQN (SEQ ID NO:31) 2: Peptide 2: SFKQNETQNMVSLKLQARLA (SEQ ID NO:32) 3: Peptide 3: SLKLQARLASSILGCGRARV (SEQ ID NO:33) 4: Peptide 4: ILGCGRARVWLDPNEAVEIQ (SEQ ID NO:34) 5: Peptide 5: DPNEAVEIQNANSRKSVRKL (SEQ ID NO:35) 6: Peptide 6: NSRKSVRKLIKDGFIIRKPV (SEQ ID NO:36) 7: Peptide 7: DGFIIRKPVKVHSRARWRKM (SEQ ID NO: 37) 8: Peptide 8: HSRARWRKMKEAKDMGRHNG (SEQ ID NO: 38) 9: Peptide 9: AKDMGRHNGVGRREGSREAR (SEQ ID NO: 39) 10 : Peptide 10 : RREGSREARMP SKELWMRRL (SEQ ID NO.- 40) 5 11: Peptide 11: SKELWMRRLRILRRLLRKYR (SEQ ID NO: 41) 12 : Peptide 12 : LRRLLRKYRADKSEDRH (SEQ ID NO: 41) Peptide 13 : KKIDRHVYRDLYMRAKGNVF (SEQ ID NO: 43) 14 : Peptide 14 : YMRAKGNVFRNKRNLVEHIH (SEQ ID NO.- 44) 15 : Peptide 15 : KRNLVEHIHKIKSEQNEKSEQKKQ: ID NO: 1015: 43) 14 : Peptide 14 : Peptide 16 : KNEKKKERQLAEQLAAKHLR (SEQ ID NO: 46) 17 : Peptide 17 : EQLAAKHLRDEQNRNKARKQ (SEQ ID NO: 47) 18 : Peptide 18 : QNRNKARKQELKSEKER (SEQ ID NO: 47) 19 : KKREKERERARRDDAAAAAQ (SEQ ID NO: 49) 20 : Peptide 20 : RDDAAAAAQKKKADAAKKSA (SEQ ID NO: 50) 15 21: Peptide 21: KADAAKKSAAPAAAKSAAPAA (SEQ ID NO: 22) AAKSAAPAAKAAPATKAAA (SEQ ID NO: 52) 23 : Peptide 23 : AAPATKAAAAPATKGAAPV (SEQ ID NO: 53) 24: Epeptide 24: PATKGAAPVKKSKK (SEQ ID NO: 54) The recombinant Leishmania major L19 protein (Lm L19) (i.e., SEQ ID No: 1) expressed in Escherichia coli was used as a control. Results Spleen cells from naive BALB / c mice (5 x 10⁶ cells / mL) were stimulated (final volume of 200 µL) with each individual peptide (100 µg / mL), with a mixture of the 24 peptides (100 µg / mL), with recombinant Leishmania major protein obtained from bacteria (12 µg / mL), and unstimulated. After 48h and 72h, the supernatants were collected and the amount of IL-10 was measured by ELISA as previously described in this document. The recombinant LmL19 obtained from bacteria was able to induce IL-10 synthesis in spleen cells of naive mice. None of the peptides were able to induce the same amount of IL-10 as the protein-induced peptide; however, statistically significant amounts of IL-10 were induced by peptides 1, 2, 12, 13, 14, 23, and 24. The level of induced IL-10 was higher 72 h after stimulation in all cases. Current experiments with peptides Experiments with newly synthesized peptides were repeated in order to confirm the results obtained. Based on these results, the same peptides were used, but three new peptides containing the sequences of the peptides that induce the highest levels of 11-10 were included. The composition of these peptides is: 25: Peptide 1-2: MTPLSLSSSRHSFKQNETQNMVSLKLQARLA (SEQ ID NO:55) : Peptide 12-13-14: LRRLLRKYRADKKIDRHVYRDLYMRAKGNVFRNKRNLVEHIH (SEQ ID NO:56) 27: Peptide 23-24: AAPATKAAAAAPATKGAAPVKKSKK (SEQ ID NO:57) Example 4: Animal Model for the study of the anti-inflammatory effect of LI9 Objective The objectives of this study are: to test the anti-inflammatory effect of our active substance derived from Lm LI 9 (i.e., SEQ ID No: 1) expressed in AND. E. coli and tested in ex vivo cultures of intestinal tissue; To investigate the anti-inflammatory effect in an animal model of Crohn's disease. Methodology To achieve these objectives, two different stages will be carried out: 1. In vitro assays with mucosal explants from patients with Crohn's disease, healthy controls, and healthy samples where inflammation was induced in vitro with PMAionomycin. After hours of incubation of the samples with the active substance, the supernatants will be analyzed for the presence of pro-inflammatory cytokines, regulatory cytokines, and chemokines, such as TNFα, IL-10, etc. RNA will be extracted from different tissues to analyze the expression of genes that encode cytokines, chemokines, transcription factors, and inflammatory signals. The tissues will be digested to obtain mucosal mononuclear cells, where the expression of certain cellular markers will be studied in order to analyze the different states of dendritic cells after incubation. The lymphocyte population will also be investigated in order to determine the specificity of the response to the active substance. 2. In vivo study of the anti-inflammatory effect of the active substance using murine inflammatory models in which chronic colitis is induced in animals by ingesting 10 potassium water with dextran sodium sulfate (DSS) for several days. The active substance will be inoculated subcutaneously into the animals before and after treatment with DSS. Different parameters, such as quantitative assessment of intestinal inflammation, will be measured to assess intestinal injury 15 (14) to (25). References 1. Zhou, X., et al, Current Drug Targets - Immune, Endocrine & Metabolic Disorders. 5(4), 2005, 465-475 2. Toshiyuki Y. , et al, European Journal of Pharmacology. 533, 2006, 289-301 3. Weiss E., et al, Journal of the American Academy of Dermatology, 50(5), 2004, 657-675 4. Wan-Wan L., et al, The Journal of Clinical Investigation 117(5), 2007, 1175-83. 5. Wooley, Curr.Opin. Rheum. 3:407-20, 1999. 6. van Riel P.L.C.M., (2001), Best Practice & Research Clinical Rheumatology, 15: 67-76. 7. Gester A.M., (1999), Bailliêre's Clinical Immunology, 13: 629-644. 8. Neurath et al. Intern. Rev. Immunol. 19:51-62, 2000 . 9. Ann Rheum Dis 2005; 64 (Suppl II) : ÍÍ65-Ü68 . doi: 10.1136 / ard.2004.031237) 10. Hongbo Y. , et al, Journal of Investigative Dermatology (2005) 125, 659-664. 11. Kirby B., et al, Br J Dermatol 2000;142:728-32. 12. Remington: The Science and Practice of Pharmacy, 20th Edition. Baltimore, MD: Lippincott Williams & Wilkins, 2000) . 13. Zhou X. Et al, (2005), Curr. Drug Targets Immune Endocr. Metabol. Disord., 5(4): 465-475. 14. Sartor R.B., Gastroenterology 2008; 134(2):577-94. 15. Bbrruel N., et al, Gut 2002; 51: 659-664. 16. Borruel N. , et al, Am J Gastroenterol 2003; 98: 865-870. 17. Carol M. , et al, J Leukocyte Biol 2006; 79: 917922. I 18. Munoz-Provencio D., et al, Arch Microbiol. 2008 Oct 31. 19. Llopis M., et al, Inflamm Bowel Dis. 2009; 15: 275-283. 20. Lugea A., et al, Gut 2000; 46: 515-521. 21. Videla S., et al, Am J Gastroenterol 2001; 96: 1486-1493. 22. Medina C., et al, Scand J Gastroenterol 2001; 36: 1314-1319.) 23. Medina C. , et al, Am J Physiol 2003; 284: G116G122 . 24. Jvidela S., et al, J Pharmacol Exp Ther. 2006; 316: 940-945. 25. Videla S., et al, Dig Dis Sci 2007;52:45-51.

Claims

1. Use of a nucleic acid molecule characterized by the fact that it is in the preparation of a medicament for the prevention or treatment of an inflammatory disorder or any condition in which inflammation occurs at a given stage of the condition in an individual, wherein said nucleic acid molecule is represented by the nucleotide sequence SEQ ID NO:

2.

2. Use of a polypeptide encoded by a nucleic acid molecule as described in claim 1, characterized in that it is in the preparation of a medicament for the prevention or treatment of an inflammatory disorder or any condition in which inflammation occurs at a given stage of the condition in an individual.

3. Use of a nucleic acid construct comprising a nucleotide sequence as described in claim 1, characterized in that it is in the preparation of a medicament for the prevention or treatment of an inflammatory disorder or any condition in which inflammation occurs at a given stage of the condition in an individual.

4. Use of a nucleic acid molecule or a polypeptide or a nucleic acid construct, according to any of claims 1 to 3, characterized by the fact that said nucleic acid molecule or said polypeptide is derived from or originates from Leishmania major, Leishmania braziliensis, Leishmania infantum, Leishmania mexicana or Leishmania donovani.

5. Use, according to any of claims 1 to 4, characterized in that the inflammatory disorder is rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease including Crohn's disease or ulcerative colitis, hepatitis, sepsis, alcoholic liver disease and non-alcoholic steatosis, sarcoidosis, autoimmune diabetes, diabetes mellitus, uveitis, multiple sclerosis, control of allograft rejection after organ transplantation, graft-versus-host disease (GVHD), inflammatory lung diseases including asthma and chronic obstructive pulmonary disease (COPD) (2), cancer (4) systemic lupus erythematosus, SLE, sarcoidosis, atopic dermatitis and cancer.

Images