Inhibitor of inflammatory cytokine-induced inflammatory reaction

Abstract

The present invention relates to an inflammatory reaction inhibitor that contains sialyllactose or a salt thereof as an active ingredient and suppresses an inflammatory cytokine-induced inflammatory reaction.

Description

Inhibitor of inflammatory cytokine-induced inflammatory response

[0001] The present invention relates to an agent for suppressing inflammatory responses induced by inflammatory cytokines.

[0002] Cytokines are important regulators of inflammation and are a general term for low-molecular-weight proteins secreted primarily by immune cells. Cytokines include pro-inflammatory cytokines and anti-inflammatory cytokines. In particular, pro-inflammatory cytokines are produced in response to pathogen invasion into the body and act on various types of cells involved in host defense, causing an inflammatory response. For example, interferon gamma (IFNγ), a human type II interferon (IFN), is a pleiotropic cytokine with diverse physiological activities in inflammatory responses to viral and certain bacterial infections, as well as in innate and adaptive immunity. IFNγ is primarily secreted by T cells and natural killer cells, and induces an inflammatory response by binding to the IFNγ receptor expressed on the cell surface of many immune system cells. As a result, it is known to enhance inflammatory responses by leukocytes (Non-Patent Document 1), increase the expression of MHC class I antigens (Non-Patent Document 2), and activate macrophages (Non-Patent Document 3). Thus, it is known that the immunoregulatory mechanism by IFNγ is beneficial in maintaining homeostasis in the human body.

[0003] On the other hand, it is also known that the breakdown of immune regulatory mechanisms due to excessive production of IFNγ can cause harmful effects. For example, in systemic lupus erythematosus (SLE), an autoimmune disease characterized by an excessive immune response, serum IFNγ levels increase before the onset of the disease, suggesting that IFNγ plays an important role in SLE (Non-Patent Document 4). It is also known that IFNγ expression is elevated in inflammatory bowel diseases (IBDs) and contributes to the exacerbation of the disease (Non-Patent Documents 5 and 6). Furthermore, abnormal activation of macrophages stimulated by IFNγ may induce chronic inflammatory diseases such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and various neurodegenerative diseases, including Alzheimer's disease (Non-Patent Documents 7-10). As exemplified by IFNγ, it is known that the breakdown of normal control of inflammatory cytokine-dependent immune responses can cause various diseases.

[0004] On the other hand, infants and young children, whose immune regulatory mechanisms are immature, and elderly people, whose immune regulatory mechanisms are weakened, are thought to be prone to chronic inflammatory states due to persistent excessive immune responses caused by certain viral and bacterial infections. Therefore, regulating inflammatory cytokine-dependent immune responses is also extremely important for maintaining the health of healthy individuals.

[0005] Kang, LJ., et al. “3’-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models.” Sci Rep 10, 5603 (2020).Zhou F. “Molecular mechanisms of IFN-gamma to up-regulate MHC class I antigen processing and presentation.” Int Rev Immunol. 2009;28(3-4):239-60.Wu C, Xue Y, et al., “IFN-γ primes macrophage activation by increasing phosphatase and tensin homolog via down regulation of miR-3473b.” J Immunol. 2014 Sep 15;193(6):3036-44.Munroe ME, Lu R, et al., “Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification.” Ann Rheum Dis.2016 Nov;75(11):2014-2021.Bouma G, et al., “The immunological and genetic basis of inflammatory bowel disease.” Nat Rev Immunol. 2003Jul;3(7):521-33.Ito R, et al., “Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice.”Clin Exp Immunol. 2006 Nov;146(2):330-8.Tipping PG, et al., “Tumor necrosis factor production by glomerular macrophages in anti-glomerular basement membrane glomerulonephritis in rabbits.” Lab Invest. 1991Sep;65(3):272-9.Kinne RW, et al., “Macrophages in rheumatoid arthritis.” Arthritis Res. 2000;2(3):189-202.Tabas, Ira A. “Consequences and Therapeutic Implications of Macrophage Apoptosis in Atherosclerosis: The Importance of Lesion Stage and Phagocytic Efficiency.” Arteriosclerosis, Thrombosis, and Vascular Biology 25 (2005): 2255-2264. Leung R, et al., “Inflammatory proteins in plasma are associated with severity of Alzheimer's disease.” PLoS One. 2013 Jun 10;8(6):e64971.

[0006] An object of the present invention is to provide an inflammatory response suppressant for suppressing inflammatory responses induced by inflammatory cytokines.

[0007] The present inventors discovered that when an inflammatory response was induced in small intestinal organoids produced in vitro using various cytokines such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-17A (IL-17A), interleukin-22 (IL-22), or IFNγ, sialyllactose suppressed the expression of genes (IL-1β, PIgR) that promote these inflammatory responses, leading to the completion of the present invention.

[0008] That is, the present invention relates to, for example, the following inventions. [1] An inflammatory response inhibitor that suppresses an inflammatory cytokine-induced inflammatory response, comprising sialyllactose or a salt thereof as an active ingredient. [2] The inflammatory response inhibitor according to [1], wherein the inflammatory cytokine is at least one selected from the group consisting of tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-17A (IL-17A), interleukin-22 (IL-22), and interferon gamma (IFNγ). [3] The inflammatory response inhibitor according to [1] or [2], wherein the inflammatory cytokine is IFNγ and the sialyllactose is 3'-sialyllactose. [4] Use of sialyllactose or a salt thereof in the manufacture of an inflammatory response inhibitor that suppresses an inflammatory cytokine-induced inflammatory response. [5] Sialyllactose or a salt thereof for use as an inflammatory response inhibitor that suppresses an inflammatory cytokine-induced inflammatory response. [6] A method for suppressing an inflammatory response induced by an inflammatory cytokine, comprising administering sialyllactose or a salt thereof. [7] Sialyllactose or a salt thereof for use in suppressing an inflammatory response induced by an inflammatory cytokine. [8] A method for preventing, alleviating, or treating a condition or disease caused by an inflammatory response induced by an inflammatory cytokine in a subject, comprising administering an effective amount of sialyllactose or a salt thereof to a subject in need thereof. [9] A composition for suppressing an inflammatory response, which contains sialyllactose or a salt thereof as an active ingredient and suppresses an inflammatory response induced by an inflammatory cytokine.

[0009] According to the present invention, inflammatory cytokine-induced inflammatory responses can be suppressed.

[0010] 1 is a graph showing the results of examining the inhibitory effect of 3'-sialyllactose or 6'-sialyllactose on the inflammatory response induced by TNF (A) or IL-1β (B) in terms of the relative mRNA amount of IL-1β. FIG. 1 is a graph showing the results of examining the inhibitory effect of 3'-sialyllactose or 6'-sialyllactose on the inflammatory response induced by IL-17A (A) or IL-22 (B) in terms of the relative mRNA amount of IL-1β. FIG. 1 is a graph showing the results of examining the inhibitory effect of 3'-sialyllactose or 6'-sialyllactose on the inflammatory response induced by IFNγ in terms of the relative mRNA amount of PIgR. FIG. 1 is a graph showing the results of examining the inhibitory effect of 3'-sialyllactose at various concentrations on the inflammatory response induced by IFNγ in terms of the relative mRNA amount of PIgR.

[0011] Hereinafter, embodiments of the present invention will be described in detail, but the present invention is not limited to the following embodiments.

[0012] 1. Inflammatory Response Inhibitor of the Present Embodiment The inflammatory response inhibitor of the present embodiment is an inflammatory response inhibitor that suppresses inflammatory cytokine-induced inflammatory responses, and contains sialyllactose or a salt thereof as an active ingredient.

[0013] Sialyllactose is a type of human milk oligosaccharide (HMO) found in breast milk and is the major acidic oligosaccharide among HMOs. Sialyllactose is a compound formed by combining N-acetylneuraminic acid, a sialic acid, with lactose, which consists of galactose and glucose. Examples of the active ingredient sialyllactose include 3'-sialyllactose (α-NeuNAc-(2→3)-β-D-Gal-(1→4)-D-Glc) and 6'-sialyllactose (α-NeuNAc-(2→6)-β-D-Gal-(1→4)-D-Glc), with 3'-sialyllactose being preferred. In the above formula, "NeuNAc" represents N-acetylneuraminic acid, "Gal" represents galactose, and "Glc" represents glucose.

[0014] Sialyl lactose may be produced by a known chemical synthesis method, a synthesis method using microorganisms, or a purification method from whey, or may be commercially available.Sialyl lactose may also be in crystalline or non-crystalline (amorphous) form.Known chemical synthesis methods include, for example, the method described in WO 2013 / 185780.Known synthesis methods using microorganisms include, for example, the methods described in WO 2017 / 152918 and WO 2001 / 004341.Known purification methods from whey include, for example, the method described in WO 2010 / 106320.

[0015] The "salt" of sialyllactose is not particularly limited, and examples thereof include inorganic base salts such as sodium salt, potassium salt, calcium salt, magnesium salt, barium salt, and aluminum salt of sialyllactose, and organic base salts such as trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, tromethamine, [tris(hydroxymethyl)methylamine], tert-butylamine, cyclohexylamine, dicyclohexylamine, and N,N-dibenzylethylamine. Furthermore, the "salt" of sialyllactose also includes amino acid salts with basic or acidic amino acids such as arginine, lysine, ornithine, aspartic acid, and glutamic acid. The "salt" of sialyllactose may be a pharmaceutically acceptable salt, and examples of pharmaceutically acceptable salts include sodium salt, potassium salt, calcium salt, magnesium salt, lithium salt, and ammonium salt of sialyllactose.

[0016] As used herein, the term "inflammatory cytokine-induced inflammatory response" refers to an inflammatory response induced by inflammatory cytokines, and is also referred to as an inflammatory cytokine-induced inflammatory response. In vivo, inflammatory cytokines are produced and secreted by immune system cells such as activated T cells, natural killer (NK) cells, helper T cells (Th1 cells), cytotoxic T cells, and macrophages, as well as mucosal epithelial cells. Inflammatory cytokines bind to cell surface receptors and excessively activate immune cells such as macrophages and dendritic cells. Symptoms such as redness, swelling, heat, and pain appear at the site of inflammation due to the innate immune response of overactivated immune cells. As used herein, the inflammatory cytokine-induced inflammatory response includes inflammatory responses induced by endogenous inflammatory cytokines (i.e., inflammatory cytokines produced and secreted by the living body), exogenous inflammatory cytokines (inflammatory cytokines administered to the living body or added in an in vitro system), or both.

[0017] Examples of inflammatory cytokines include tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-17A (IL-17A), interleukin-22 (IL-22), interferon gamma (IFNγ), interleukin-8 (IL-18), interleukin-18 (IL-18), granulocyte colony-stimulating factor (G-CMF), chemokines, etc. The inflammatory cytokine is preferably at least one selected from the group consisting of tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-17A (IL-17A), interleukin-22 (IL-22), and interferon gamma (IFNγ), and more preferably interferon gamma (IFNγ).

[0018] The inflammatory response inhibitor of this embodiment can suppress inflammatory cytokine-induced inflammatory responses, but does not suppress inflammatory responses induced by other inflammation-inducing substances, such as histamine or serotonin. "Suppression of an inflammatory response" refers to a reduction in the inflammatory response in the presence of the inflammatory response inhibitor of this embodiment compared to the inflammatory response in the absence of the inflammatory response inhibitor of this embodiment. Indicators of inflammatory response suppression are not particularly limited, and examples include a reduction in the expression level of a gene involved in the inflammatory cytokine-induced inflammatory response. For example, the expression level of a gene involved in the inflammatory cytokine-induced inflammatory response in the presence of the inflammatory response inhibitor of this embodiment may be reduced by 10% or more, 20% or more, 30% or more, 40% or more, or 50% or more compared to the inflammatory response in the absence of the inflammatory response inhibitor of this embodiment.

[0019] Examples of genes involved in inflammatory cytokine-induced inflammatory responses include polymeric immunoglobulin receptor (pIgR), MHC II, signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and IL-1β. The expression level of a gene involved in inflammatory cytokine-induced inflammatory responses may be the amount of mRNA transcribed from the gene, or the amount of protein / polypeptide translated from the mRNA. Here, the amount of mRNA and the amount of protein / polypeptide can be measured by known methods using commercially available instruments and reagents. In the case of RNA, measurement methods include quantitative RT-PCR, quantitative real-time RT-PCR, and quantitative Northern blotting. In the case of protein, measurement methods include Western blotting, ELISA, and immunostaining.

[0020] Suppression of an inflammatory response induced by an inflammatory cytokine can be evaluated, for example, by measuring the reduction in the expression level of a gene involved in an inflammatory response induced by an inflammatory cytokine in the presence of the inflammatory response inhibitor of this embodiment compared to the absence of the inflammatory response inhibitor of this embodiment. When the inflammatory cytokine is, for example, IFNγ and the gene used for evaluation is pIgR, the expression level (mRNA amount or protein / polypeptide amount) of pIgR in the presence of the inflammatory response inhibitor of this embodiment may be reduced by 10% or more, 20% or more, 30% or more, 40% or more, or 50% or more compared to the absence of the inflammatory response inhibitor of this embodiment.

[0021] The inflammatory response inhibitor of this embodiment can be used to prevent, alleviate, or treat conditions or diseases caused by inflammatory cytokine-induced inflammatory responses (particularly excessive inflammatory responses induced by inflammatory cytokines) by suppressing inflammatory cytokine-induced inflammatory responses. Examples of such conditions or diseases include autoimmune diseases such as systemic lupus erythematosus (SLE), inflammatory bowel diseases (IBDs), rheumatoid arthritis, glomerulonephritis, atherosclerosis, and neurodegenerative diseases such as Alzheimer's disease. The inflammatory response inhibitor of this embodiment can also be used to prevent, alleviate, or treat inflammatory responses in infectious diseases such as bacterial infections and viral infections, and can be used particularly in subjects with weak immune regulatory mechanisms, such as infants and the elderly, to prevent, alleviate, or treat excessive inflammatory responses, for example, during viral infections.

[0022] The inflammatory response inhibitor of this embodiment may contain only sialyllactose and / or a salt thereof, or may contain components other than the active ingredient sialyllactose or a salt thereof as necessary. That is, the inflammatory response inhibitor of this embodiment may be an inflammatory response inhibitor composition containing an effective amount of sialyllactose or a salt thereof. Such a composition may be, for example, a food composition or a pharmaceutical composition.

[0023] The effective amount of sialyllactose or a salt thereof in the inflammatory response inhibitor of this embodiment is not particularly limited, as long as it is an amount that achieves the above-mentioned inflammatory response inhibitory effect. The effective amount may vary depending on the symptoms or disease, and may also vary depending on the purpose of prevention or treatment, and can be appropriately determined by those skilled in the art as needed. For example, for an adult weighing 60 kg (here, "adult" refers to a human aged 15 or older), the amount may be 1 mg to 50,000 mg / day in terms of sialyllactose, preferably 500 mg to 20,000 mg / day. When the inflammatory response inhibitor of this embodiment is administered to a subject, the number of administrations is not particularly limited, and may be once a day or may be divided into multiple doses, such as twice or three times a day. The timing of administration is also not particularly limited, and may be after waking up, before meals, after meals, between meals, or before bedtime. The subject may be a mammal, and preferably a human. The route of administration may be, for example, oral administration, sublingual administration, intramuscular administration, enteral administration, nasal administration, intravenous administration, subcutaneous administration, or intraperitoneal administration, with oral administration being preferred.

[0024] The food composition preferably has an emphasis on its tertiary function (biomodulation function). Examples of foods with an emphasis on their tertiary function include health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods for special dietary uses, foods with nutrient functions, and foods with functional claims. Examples of biomodulation functions include immune care, immune function support, immune function maintenance, and immune function regulation.

[0025] In addition to sialyllactose or a salt thereof, the food composition may contain other ingredients acceptable for use as food, such as carbohydrates, proteins, lipids, minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, flavorings, stabilizers, preservatives, sustained-release regulators, surfactants, solubilizers, and humectants.

[0026] The food composition may be in the form of a supplement (tablet, drink, powder, capsule, etc.), or may be in the form of a beverage, Western confectionery, Japanese confectionery, frozen dessert, cooked food, seasoning, etc., which are commonly consumed as food.

[0027] The method for producing food composition is not particularly limited, and can be appropriately according to known methods.For example, in the case of supplements, an effective amount of sialyllactose or its salt can be mixed with suitable additives and then made into a desired dosage form; in the case of adding to food, an effective amount of sialyllactose or its salt can be mixed with an intermediate product or final product in the food manufacturing process.

[0028] In addition to sialyllactose or its salt, the pharmaceutical composition may contain pharmaceutically acceptable additives such as excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, suspending agents, etc.

[0029] The pharmaceutical composition may be in any form such as a solid, liquid, or paste, and may be in the form of a tablet (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsule, pill, powder (dispersed medicine), fine granules, granules, liquid, suspension, emulsion, syrup, paste, or injection (including a case where the composition is mixed with distilled water or an infusion such as an amino acid infusion or an electrolyte infusion at the time of use to prepare a liquid).

[0030] The content of sialyllactose or a salt thereof in the inflammatory response inhibitor of this embodiment may vary depending on the form and ingestion method of the composition, but is not particularly limited as long as the content is such that the above-mentioned inflammatory response inhibitory effect can be obtained. The content of sialyllactose or a salt thereof in the inflammatory response inhibitor of this embodiment, calculated as sialyllactose, relative to the total amount of the inflammatory response inhibitor, may be, for example, 0.001% by mass or more, 0.01% by mass or more, 0.1% by mass or more, 1% by mass or more, 10% by mass or more, 50% by mass or more, 90% by mass or more, 95% by mass or more, 97% by mass or more, 98% by mass or more, 99% by mass or more, or 100% by mass. The content of sialyllactose or a salt thereof in the inflammatory response inhibitor of this embodiment, calculated as sialyllactose, relative to the total amount of the inflammatory response inhibitor, may be, for example, 100% by mass or less, 50% by mass or less, 10% by mass or less, 5% by mass or less, 3% by mass or less, 2% by mass or less, or 1% by mass or less.

[0031] [2. Use of this embodiment] One aspect of this embodiment provides the use of sialyllactose or a salt thereof in the manufacture of an inflammatory response inhibitor that suppresses inflammatory cytokine-induced inflammatory responses. Another aspect of this embodiment provides sialyllactose or a salt thereof for use as an inflammatory response inhibitor that suppresses inflammatory cytokine-induced inflammatory responses. Another aspect of this embodiment provides sialyllactose or a salt thereof for use in suppressing inflammatory cytokine-induced inflammatory responses.

[0032] 3. Method for suppressing inflammatory response of the present embodiment One aspect of this embodiment provides a method for suppressing an inflammatory response induced by an inflammatory cytokine, comprising administering sialyllactose or a salt thereof. In particular, a method for suppressing an inflammatory response induced by an inflammatory cytokine in a subject is provided, comprising administering an effective amount of sialyllactose or a salt thereof to a subject in need thereof. Another aspect of this embodiment provides a method for preventing, alleviating, or treating a condition or disease caused by an inflammatory response induced by an inflammatory cytokine in a subject, comprising administering sialyllactose or a salt thereof (preferably an effective amount of sialyllactose or a salt thereof) to a subject in need thereof. Furthermore, another aspect of this embodiment provides a method for suppressing an inflammatory response induced by an inflammatory cytokine in vitro, comprising using sialyllactose or a salt thereof.

[0033] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0034] (Test Example 1: Evaluation of the effect of suppressing inflammatory cytokine-induced inflammatory responses) Small intestinal organoids were prepared according to a previously published study (Stem cell reports 10.1 (2018): 314-328., Scientific Reports volume 13, Article number: 5407 (2023)). However, since the inside of small intestinal organoids is the luminal side, in order to mimic the stimulation from the luminal side where ingested food components are absorbed, it was necessary to introduce reagents (sialyllactose, cytokines, etc.) directly into the inside by microinjection. Therefore, in this example, the prepared small intestinal organoids were crushed and then cultured two-dimensionally to form a monolayer, exposing the luminal side. An evaluation system was used in which stimulation from the luminal side could be achieved by adding the desired reagent to the medium (EBioMedicine 23 (2017): 34-45.).

[0035] More specifically, disrupted small intestinal organoids were seeded onto collagen-coated 12-well plates and cultured in human organoid growth medium for 4 days. After 4 days, the medium was replaced with human organoid differentiation medium and cultured for 24 hours. Subsequently, 3'-sialyllactose (3'SL) or 6'-sialyllactose (6'SL) was added to a final concentration of 0.9 or 1 mg / mL, and the culture was continued for 24 hours (3'SL addition group or 6'SL addition group). Subsequently, TNF (0.3 or 1 ng / mL), IL-1β (0.1 or 1 ng / mL), IL-17A (1 or 10 ng / mL), IL-22 (1 or 10 ng / mL), or IFNγ (0.3 or 1 ng / mL) was added, and the culture was continued for another 6 hours to induce an inflammatory response. Since the enhancement of inflammatory responses induced by TNF, IL-1β, IL-17A, and IL-22 can be quantified by measuring the expression level of the IL-1β gene, RNA was extracted from cells after induction of an inflammatory response, and the relative mRNA level of IL-1β was measured by real-time PCR. Furthermore, since the enhancement of inflammatory responses induced by IFNγ can be quantified by measuring the expression level of the PIgR gene, RNA was extracted from cells after induction of an inflammatory response, and the relative mRNA level of the PIgR gene was measured by real-time PCR. The mRNA level of 18S rRNA was used as an internal standard to measure the relative mRNA levels of IL-1β and PIgR genes. Furthermore, the relative mRNA levels of IL-1β and PIgR genes were measured by real-time PCR in the same manner except that sialyllactose was not added (control group). The results are shown in Figures 1 to 3.

[0036] As shown in Figures 1 and 2, when an inflammatory response was induced with 0.3 ng / mL of TNF, the relative mRNA levels of the IL-1β gene were reduced compared to the control group in the 3'SL-added group and the 6'SL-added group, and in the 3'SL-added group when an inflammatory response was induced with 1 ng / mL of TNF. The relative mRNA levels of the IL-1β gene were reduced compared to the control group in the 6'SL-added group when an inflammatory response was induced with 0.1 ng / mL of IL-1β, and in the 3'SL-added group when an inflammatory response was induced with 1 ng / mL of IL-1β. The relative mRNA levels of the IL-1β gene were reduced compared to the control group in the 3'SL-added group and the 6'SL-added group when an inflammatory response was induced with 10 ng / mL of IL-17A. When an inflammatory response was induced with 10 ng / mL of IL-22, the relative mRNA level of the IL-1β gene was reduced in the 6'SL-added group compared to the control group.

[0037] Furthermore, as shown in Figure 3, the relative mRNA level of the PIgR gene was reduced compared to the control group in the 3'SL-added group when an inflammatory response was induced with 0.3 ng / mL of IFNγ, and in the 3'SL-added and 6'SL-added groups when an inflammatory response was induced with 1 ng / mL of IFNγ. In particular, the relative mRNA level of the PIgR gene was significantly lower in the 3'SL-added group when an inflammatory response was induced with 1 ng / mL of IFNγ compared to the control group. These results demonstrate that 3'SL and 6'SL have the effect of suppressing TNF-induced inflammatory responses, IL-1β-induced inflammatory responses, IL-17A-induced inflammatory responses, IL-22-induced inflammatory responses, and IFNγ-induced inflammatory responses. In particular, 3'SL was found to have the effect of significantly suppressing IFNγ-induced inflammatory responses.

[0038] (Test Example 2: Evaluation of the effect of suppressing IFNγ-induced inflammatory response at different concentrations of 3′SL) An experiment similar to Test Example 1 was carried out, except that the amount of 3′SL added was 0.5 mg / mL, 1 mg / mL, or 2 mg / mL. The results are shown in FIG.

[0039] As shown in FIG. 4, the inhibitory effect of 3'SL on IFNγ-induced inflammatory responses was confirmed at all added amounts of 0.5 mg / mL or more.

Claims

1. An inflammatory response suppressant which contains sialyllactose or a salt thereof as an active ingredient and suppresses inflammatory responses induced by inflammatory cytokines.

2. The inflammatory response suppressant according to claim 1, wherein the inflammatory cytokine is at least one selected from the group consisting of tumor necrosis factor (TNF), interleukin-1β (IL-1β), interleukin-17A (IL-17A), interleukin-22 (IL-22) and interferon gamma (IFNγ).

3. The inflammatory response inhibitor according to claim 2, wherein the inflammatory cytokine is IFNγ and the sialyllactose is 3'-sialyllactose.

4. Use of sialyllactose or a salt thereof in the manufacture of an inflammatory response inhibitor that suppresses inflammatory cytokine-induced inflammatory responses.

5. Sialyllactose or a salt thereof for use in suppressing inflammatory responses induced by inflammatory cytokines.

6. A method for suppressing an inflammatory response induced by inflammatory cytokines, comprising administering sialyllactose or a salt thereof.

7. A method for preventing, alleviating or treating a condition or disease caused by an inflammatory cytokine-induced inflammatory response in a subject, comprising administering an effective amount of sialyllactose or a salt thereof to a subject in need thereof.