Application of adenosine in preparation of medicine for preventing chronic obstructive pulmonary disease

Abstract

The invention discloses an application of adenosine in preparing or preventing a chronic obstructive pulmonary disease, the chronic obstructive pulmonary disease refers to an acute exacerbation stage of the chronic obstructive pulmonary disease, and the acute exacerbation stage of the chronic obstructive pulmonary disease is caused by streptococcus pneumoniae; the medicine is used for inhibiting cell activation and proinflammatory factor release through an A2AR receptor. The invention provides a powerful scientific basis for application of adenosine in preparation of related drugs in treatment and prevention of lung diseases, especially chronic obstructive pulmonary diseases.

Description

Technical Field

[0001] This invention belongs to the pharmaceutical field and relates to drugs for chronic obstructive pulmonary disease (COPD), specifically the application of adenosine in the preparation or prevention of COPD drugs. Background Technology

[0002] Chronic obstructive pulmonary disease (COPD) is a chronic lung disease characterized by persistent airflow limitation, mainly manifested as shortness of breath, chronic cough and sputum production, and its airflow obstruction is usually irreversible.

[0003] Intervention with Streptococcus pneumoniae can exacerbate the occurrence and development of COPD. This is mainly because the intervention with Streptococcus pneumoniae increases the release of inflammatory cytokines, leading to alveolar epithelial damage, decreased lung function, and increased expression of platelet-activating factor receptor and bacterial load. This will significantly increase the risk of acute exacerbations in COPD patients.

[0004] The pathogenesis of COPD involves chronic inflammation, oxidative stress, and irreversible damage to lung structure and function. Currently, there is no cure; treatment focuses on slowing disease progression, improving symptoms, and enhancing patients' quality of life.

[0005] Endogenous metabolites, as naturally produced bioactive molecules, play a crucial role in regulating inflammation, oxidative stress, and immune responses. The precise discovery of endogenous metabolites offers new avenues for the treatment of CODP and its associated adverse events of COPD (adverse reactions to COPD). By targeting core pathophysiological mechanisms, endogenous metabolites overcome the limitations of traditional symptomatic treatments. Furthermore, due to their low toxicity and high safety profile, endogenous metabolites can utilize the body's inherent metabolic system to reduce side effects. The main challenges currently facing the body are further exploring the dynamic regulation of metabolic networks, developing efficient delivery systems, and validating their clinical translational potential through clinical trials. Summary of the Invention

[0006] The purpose of this invention is to precisely identify potentially beneficial endogenous metabolites by comparing significantly different metabolites in normal and COPD groups and their acute exacerbations through metabolomics and microbiome analysis. Based on existing analysis, adenosine has been preliminarily identified as a metabolite that may have a therapeutic effect on Streptococcus pneumoniae-induced acute exacerbations of COPD. Subsequent in vivo and in vitro experiments will be used to evaluate its efficacy, with the aim of reducing inflammation and restoring lung function.

[0007] The specific technical solution of the present invention includes: the application of adenosine in the preparation or prevention of drugs for chronic obstructive pulmonary disease.

[0008] Preferably, the chronic obstructive pulmonary disease refers to the acute exacerbation of chronic obstructive pulmonary disease.

[0009] More preferably, the acute exacerbation of chronic obstructive pulmonary disease is caused by Streptococcus pneumoniae.

[0010] Preferably, the drug is a drug that inhibits cell activation and the release of pro-inflammatory factors through the A2AR receptor.

[0011] Adenosine is an endogenous nucleoside found throughout human cells. It can directly enter the myocardium, be phosphorylated to produce adenosine monophosphate, and participate in myocardial energy metabolism. It also participates in dilating coronary arteries and increasing blood flow. Recent studies have found that adenosine shows potential therapeutic effects in immunomodulation. Adenosine can inhibit cell activation and the release of pro-inflammatory factors through the A2AR receptor, exerting an anti-inflammatory effect and potentially being used to treat autoimmune diseases or reduce tissue damage.

[0012] Preferably, the adenosine is a compound formed by linking the N-9 of adenine and the C-1 of D-ribose via a β-glycosidic bond.

[0013] Preferably, the dosage of the adenosine administered in animal experiments is 1-10 mg / kg.

[0014] Preferably, the concentration of adenosine in in vitro cell experiments is 1-10 μM.

[0015] Preferably, the dosage form of the drug is any one of tablets, capsules, granules, powders, or liquid preparations.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0017] 1. The endogenous metabolite adenosine of this invention is based on the results of comparative microbiome and metabolomics analysis. This metabolite adenosine has anti-inflammatory and tissue-damage-reducing effects. Furthermore, this metabolite adenosine can avoid systemic side effects and improve treatment safety.

[0018] 2. The endogenous metabolite adenosine of this invention exhibits significant therapeutic effects in a mouse model of chronic obstructive pulmonary disease (COPD) and its acute exacerbations. HE staining and pathological analysis showed that nasal inhalation of adenosine effectively reduced lung inflammation, decreased inflammatory cell infiltration and mucus secretion in mice, and significantly improved lung function. Furthermore, ELISA and qPCR results consistently showed a significant reduction in the levels of inflammatory factors (such as TNF-α, IL-6, and IL-1β) in the lung tissue of treated mice, further validating the therapeutic effect. This provides strong scientific evidence for the application of endogenous metabolite adenosine in the preparation of related drugs for the treatment and prevention of lung diseases, especially COPD.

[0019] 3. The endogenous metabolite adenosine of this invention also exhibited inhibitory effects on the expression of inflammatory factors and reduced cellular inflammation levels in in vitro cell experiments. In MH-S and MLE12 cells, the expression levels of pro-inflammatory factors such as IL-6, TNF-α, and IL-1β decreased after treatment with adenosine. Metabolite functional enrichment analysis showed significant involvement of the cAMP signaling pathway, suggesting that adenosine may play a role in immune regulation by activating the cAMP signaling pathway, promoting the phosphorylation of its downstream proteins, and then exerting an anti-inflammatory effect. Secretory proteomics analysis of the cell supernatant further revealed the effects of adenosine treatment on lung epithelial cells, which will reveal the regulatory mechanism of endogenous metabolite adenosine in respiratory diseases, especially its regulatory role in the pathological process of chronic obstructive pulmonary disease, providing theoretical support at the molecular pharmacological level for its clinical translational application.

[0020] 4. The drug formulation developed in this invention can be a liquid reagent that can be inhaled via nebulization. In the treatment of lung diseases, nebulized inhalers can deliver the drug directly to the respiratory mucus and alveoli, resulting in a high drug concentration in local tissues and thus exerting a therapeutic effect. As a method of local respiratory administration, compared with systemic administration, it avoids drug degradation by the gastrointestinal tract and the first-pass effect of the liver, therefore systemic adverse reactions are less common. Attached Figure Description

[0021] Figure 1 In this embodiment of the invention, the wet-to-dry ratio of mouse lung tissue reflects the improvement of COPD pulmonary edema by the metabolite adenosine.

[0022] Figure 2 HE staining of mouse lung tissue sections in this embodiment of the invention reflects the improvement of COPD lung pathology by metabolites.

[0023] Figure 3 This is a schematic diagram illustrating how the total protein in the bronchoalveolar lavage fluid of mice reflects the reduction of total protein in the bronchoalveolar lavage fluid of COPD mice by the metabolite adenosine in an embodiment of the present invention.

[0024] Figures 4 to 7 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in lung tissue, as demonstrated by an RT-qPCR experiment in mouse lung tissue in this embodiment of the invention.

[0025] Figures 8 to 10 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in lung tissue in a mouse lung tissue ELISA experiment, as described in this embodiment of the invention.

[0026] Figure 11 This is a schematic diagram illustrating the effect of different concentrations of the metabolite adenosine on the growth and reproduction of MH-S cells.

[0027] Figure 12This is a schematic diagram illustrating the effects of different concentrations of the metabolite adenosine on the growth and reproduction of MLE12 cells.

[0028] Figures 13 to 15 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in MH-S cells, as demonstrated in an MH-S cell RT-qPCR experiment of this invention.

[0029] Figures 16 to 18 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in MLE12 cells, as demonstrated by an RT-qPCR experiment in this embodiment of the invention.

[0030] Figures 19 to 21 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in cells, as demonstrated by the MH-S cell ELISA experiment in this embodiment of the invention.

[0031] Figures 22 to 23 This is a schematic diagram illustrating how the metabolite adenosine reduces the expression of inflammatory factors in MLE12 cells, as demonstrated by an ELISA experiment in this invention. Detailed Implementation

[0032] This invention proposes an endogenous metabolite, adenosine, to address a key issue in the treatment of chronic obstructive pulmonary disease (COPD). Adenosine inhibits the release of pro-inflammatory cytokines and regulates immune cell activation, enabling targeted anti-inflammatory therapy through in vivo nasal drop administration and in vitro cell-based administration.

[0033] Endogenous adenosine metabolites exhibited good physiological activity in mouse models, effectively reducing lung inflammation and improving lung dysfunction, and had clear targeting, reducing the risk of damage to other organs.

[0034] This invention offers a novel perspective on the treatment of chronic obstructive pulmonary disease (COPD). By modulating immune responses and reducing inflammation to improve lung function, it holds promise for fundamentally improving the quality of life for COPD patients. Future research is expected to enable the widespread clinical application of this endogenous-based innovative drug, bringing new hope to COPD patients.

[0035] The present invention will be further described below with reference to the accompanying drawings and embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of the present invention.

[0036] Example 1: Study on the anti-inflammatory effect of the metabolite adenosine in vivo

[0037] 1.1 Establishing experimental animal models

[0038] C57BL / 6 mice were purchased from Vital River Laboratory Animal Co., Ltd. Six-week-old male mice, weighing approximately 20-22g, were selected and housed in an SPF (Special Protected Forest) environment. The mice underwent regular 12-hour light / dark cycles at a room temperature of 20-25°C and a relative humidity of 50-70%. This ensured the maintenance of the mice's circadian rhythm while preserving their normal physiological and behavioral performance. In this study, a series of experimental groups were designed to evaluate the efficacy of the metabolite adenosine in the treatment of chronic obstructive pulmonary disease (COPD) and its anti-inflammatory mechanism.

[0039] Thirty male C57BL / 6 mice were randomly divided into 5 groups.

[0040] Control group: 20 μL of phosphate-buffered saline (PBS) was instilled intranasally every three days for 6 weeks.

[0041] Disease group: A suspension containing 350 μg / kg lipopolysaccharide (LPS) and 60 U / kg elastase (PPE) was instilled into the nose every six days, with a total volume of 20 μL, for 6 consecutive weeks.

[0042] Disease exacerbation: Mice were administered a nasal suspension containing 350 μg / kg lipopolysaccharide (LPS) and 60 U / kg elastase (PPE) every six days, with a total volume of 20 μL, for six consecutive weeks. Following this, mice were further exacerbated by nasal administration of Streptococcus pneumoniae (Sp) to exacerbate the disease, a single treatment at a Streptococcus pneumoniae bacterial concentration of 10. 8 CFU / 20uL.

[0043] In the nasal drop therapy group, mice were initially treated with a mixture of 350 μg / kg LPS and 60 U / kg PPE via nasal drops every six days, at a dose of 20 μL each time, for six consecutive weeks. In addition, mice received further nasal drop therapy with adenosine every three days for six weeks. The adenosine concentration was set at 10 mg / kg.

[0044] In a disease exacerbation treatment regimen, mice were initially treated with a mixture of 350 μg / kg LPS and 60 U / kg PPE via nasal drops every six days at a dose of 20 μL for six weeks. Following this, mice were further treated with a single dose of Streptococcus pneumoniae (Sp) via nasal drops. In addition, mice received adenosine via nasal drops every three days for six weeks. Notably, mice following the Streptococcus pneumoniae nasal drop received an additional dose of adenosine via nasal drops, once daily for three consecutive days. The Streptococcus pneumoniae bacterial concentration was set at 10... 8CFU / 20uL, adenosine concentration set at 10mg / kg.

[0045] 1.2. HE staining of mouse lung tissue sections

[0046] Lung tissue samples were collected from each group of mice. The lung tissue was first rinsed briefly with PBS, then fixed in 4% paraformaldehyde solution at room temperature for 24 hours. Subsequently, the tissue was embedded in paraffin through dehydration, clearing, and paraffin infiltration. The paraffin-embedded tissue was then sectioned and stained with hematoxylin and eosin (HE staining). The HE-stained lung tissue sections were observed and scored, with particular attention paid to alveolar inflammation.

[0047] Alveolar inflammation score: Counts and assesses the number and distribution of inflammatory cells in the alveoli and interstitium. No inflammatory infiltration is 0 points; mild inflammatory infiltration is 1 point; a large number of inflammatory cells with uneven distribution is 2 points; a large number of inflammatory cells with even distribution but not aggregated is 3 points; a large number of inflammatory cells with aggregated clusters is 4 points.

[0048] like Figure 2 The results showed that nasal drops containing the metabolite adenosine reduced inflammatory cell infiltration and alleviated lung inflammation.

[0049] 1.3 Determination of total protein (BCA) in mouse bronchoalveolar lavage fluid

[0050] 1) Collection of bronchoalveolar lavage fluid

[0051] First, thread two surgical sutures between the trachea and esophagus. Then, insert the indwelling intravenous cannula into the trachea and tie it tightly at the point where the cannula enters the trachea and at the distal end of the cannula. Connect a 1mL syringe to irrigate 0.5mL of the cannula, leave it for 30 seconds, and slowly aspirate. Repeat this process 3 times.

[0052] 2) Determination of BCA

[0053] Sample preparation: The collected mouse bronchoalveolar lavage fluid was centrifuged at low temperature to remove the sediment at the bottom of the tube and obtain the supernatant sample of the lavage fluid.

[0054] After preparing protein standards, setting the concentration gradient of the standard curve, preparing BCA working solution, determining the protein concentration of the samples, and drawing the standard curve, the data were analyzed. Based on the standard curve and the OD value of the samples, the concentration of total protein in the bronchoalveolar lavage fluid was calculated and statistically analyzed.

[0055] like Figure 3 The results showed that after treatment with the metabolite adenosine, the total protein content of bronchoalveolar lavage fluid in diseased and disease-adjusted mice decreased.

[0056] 1.4 RT-qPCR assay for detecting inflammatory factors in lung tissue

[0057] 1) Extracting RNA from tissues

[0058] Lung tissue was harvested from euthanized mice. The tissue sample was weighed, ground in lysis buffer, and allowed to stand at room temperature for 5 minutes. An equal volume of anhydrous ethanol was added, and the mixture was thoroughly stirred. The sample mixture was added to a centrifuge tube and centrifuged at 4000xg for 1 minute at room temperature. 500 μL of washing buffer was added to the centrifuge tube, and the mixture was centrifuged at 12000xg for 1 minute at room temperature. The centrifuge tube was transferred to a new EP tube, left uncapped and allowed to air dry for 2 minutes. 20-30 μL of washing buffer was added to the centrifuge tube, and the mixture was centrifuged at 12000xg for 1 minute at room temperature. The centrifuge tube was discarded; the centrifuged product was RNA.

[0059] 2) Total RNA reverse transcription

[0060]

[0061] Reverse transcription reaction conditions: 50℃ for 15 minutes, 85℃ for 5 seconds, cDNA is obtained after the reverse transcription stage is completed.

[0062] 3) RT-qPCR test

[0063] Dilute the cDNA obtained above 5 times with sterile ddH2O to prepare the qPCR reaction system:

[0064]

[0065]

[0066] Centrifuge the qPCR plate in a centrifuge for 2 minutes before testing.

[0067] 4) Analysis of experimental results

[0068] Calculation formula:

[0069] △Ct = Ct (target gene) - Ct (internal reference gene)

[0070] △△Ct = △Ct (experimental group) - △Ct (control group)

[0071] RQ=2- △△Ct

[0072] like Figures 4 to 7 The results showed that the adenosine-treated mice exhibited reduced inflammation in terms of the mRNA expression levels of TNF-α, IL-6, CXCL-15, and IL-1β.

[0073] 1.5 ELISA assay for detecting inflammatory factors in lung tissue

[0074] To quantitatively detect the expression levels of cytokine proteins in mouse lung tissue homogenates, enzyme-linked immunosorbent assay (ELISA), a standardized biochemical analysis method, was used.

[0075] Sample preparation: The collected mouse lung tissue samples were processed appropriately and homogenized using a tissue homogenizer to obtain homogenized samples.

[0076] After preparing the cytokine standard curve, antibody coating, blocking, adding samples and standards, adding detection antibodies, adding substrates, stopping the reaction, and measuring optical density, the data were analyzed. Based on the standard curve and the OD value of the samples, the concentration of cytokines in the lung tissue homogenate was calculated and statistically analyzed.

[0077] like Figures 8 to 10 The results showed that the protein expression levels of TNF-α, IL-1β, and IL-6 decreased after adenosine treatment.

[0078] Example 2: Establishing a cell model and detecting the content of inflammatory factors in cells

[0079] 2.1 Effects of different concentrations of adenosine metabolites on cells

[0080] MH-S cells and MLE12 cells in the logarithmic growth phase were harvested at a concentration of 1×10⁻⁶. 4 Cells were seeded into two 96-well plates, and 100 µL of RPMI 1640 and DMEM F12 complete medium were added to each well, respectively. The cells were cultured at 37°C with 5% CO2 until the density reached 30%. The old medium was discarded, and 100 µL of adenosine solutions of different concentrations (0 μM (NC), 5 μM, 10 μM, 25 μM, 50 μM, 100 μM) were added. CCK-8 reagent was added at a 1:10 ratio according to the medium volume, and the plates were incubated at 37°C for 4 hours. The absorbance was measured at 450 nm using a microplate reader.

[0081] like Figure 11 and Figure 12 The results showed that different concentrations of adenosine had either promoting or inhibiting effects on cell growth, and 10 μm adenosine had no effect on cell growth and reproduction. Therefore, a 10 μm adenosine solution was selected for subsequent experiments.

[0082] 2.2 Establishment of Cell Model

[0083] MH-S cells and MLE12 cells need to be stored in RPMI1640 and DMEMF12 media, respectively, with the addition of 10% fetal bovine serum and penicillin (100µg / mL)-streptomycin (100µg / mL), and cultured at 37°C in a humid environment with 5% carbon dioxide.

[0084] Preparation of the modeling solution: Commercially available Double Happiness cigarettes were used. CSE (smoke extract) was prepared using a CSE preparation apparatus (including a sterile operating table, smoking device, sterile collection device, absorbent, and cigarettes). The preparation process was as follows: 10 cigarettes were lit, and the smoke was guided through a sterile catheter into a volume containing 50 mL of DMEM. Continuous inhalation was performed using a syringe-driven device, ensuring each cigarette burned for 5 minutes. The dissolution rate of the smoke in the absorbent was matched to the inhalation speed to ensure that the chemical components in the smoke dissolved in the DMEM medium. One cigarette was extracted per 10 mL of medium. The pH of the extract was adjusted to 7.4 ± 0.5, and undissolved particulate matter was removed by sterile filtration (0.22 µm filter membrane) to obtain 100% CSE stock solution.

[0085] Model establishment and application: MH-S and MLE12 cells in logarithmic growth phase were used at a concentration of 5 × 10⁻⁶ cells / year. 6 The cells were seeded into two 6-well plates. After the cells adhered to the plates and grew to a density of 50%, the medium was changed.

[0086] In this application, we designed a series of cell experimental groups with the aim of thoroughly evaluating the efficacy of the metabolite adenosine in the treatment of chronic obstructive pulmonary disease (COPD).

[0087] Control group: Discard the old complete cell culture medium and replace it with new 2 mL of complete cell culture medium containing penicillin (100 µg / mL) - streptomycin (100 µg / mL) 2% fetal bovine serum.

[0088] Disease group: Discard the old complete cell culture medium and replace it with 2 mL of new 0.075% CSE medium containing penicillin (100 µg / mL), streptomycin (100 µg / mL) and 2% fetal bovine serum.

[0089] Disease-additional combination: Discard the old complete cell culture medium and replace it with 2 mL of new 0.075% CSE culture medium containing penicillin (100 µg / mL) - streptomycin (100 µg / mL) and 2% fetal bovine serum. In addition, add 5 µL of Sp bacterial suspension (take 1 mL of logarithmic growth phase Streptococcus pneumoniae, centrifuge and resuspend in an equal volume of PBS for later use).

[0090] Adenosine-treated disease group: Discard the old complete cell culture medium and replace it with a new 2 mL of 10 μm adenosine culture medium containing penicillin (100 µg / mL), streptomycin (100 µg / mL) and 0.075% fetal bovine serum, and add 1.5 µL of CSE stock solution.

[0091] Adenosine-treated disease plus combination: Discard the old complete cell culture medium and replace it with a new 2.5 mL of 10 μm adenosine culture medium containing penicillin (100 µg / mL) - streptomycin (100 µg / mL) and 0.075% fetal bovine serum, and add 1.5 µL of CSE stock solution and 5 μL of Sp suspension.

[0092] After culturing each group of cells in a humid environment of 37°C and 5% carbon dioxide for 24 hours, the culture was terminated.

[0093] 2.3 RT-qPCR assay for detecting inflammatory factor levels in cells

[0094] 1) Extracting RNA from tissues

[0095] MH-S cells and MLE12 cells were seeded in 6-well plates, respectively. After 12 hours, modeling medium, bacterial suspension, and adenosine were added to the 6-well plates according to the above grouping. After 24 hours, when the cell confluence reached 90%, the culture medium was discarded. Cells were washed with PBS, and 500 μL of lysis buffer was added. The plates were shaken at room temperature for 1–2 minutes, and an equal volume of anhydrous ethanol was added. After thorough mixing, the mixture was transferred to a centrifuge column and centrifuged at 4000g for 2 minutes. The liquid was discarded, and 500 μL of washing buffer was added. The plates were centrifuged at 12000g for 2 minutes. The centrifuge column was then transferred to a new RNase-free EP tube. 25 μL of elution buffer was added to the centrifuge column, the cap was opened, and the tube was incubated for 3 minutes. The tube was then centrifuged at 12000g for 2 minutes. The resulting liquid was the extracted total RNA.

[0096] 2) RT-qPCR

[0097] The procedures for RNA reverse transcription and RT-qPCR are the same as those in 1.4 of Example 1.

[0098] like Figures 13 to 18 The results showed that the expression of TNF-α, IL-6, and IL-1β in the MH-S cell adenosine treatment group was significantly lower than that in the disease group and the disease-additive group. We also obtained similar results of inflammation reduction in MLE12 cells.

[0099] 2.4 ELISA assay to detect the content of inflammatory factors in cell supernatant

[0100] To quantitatively detect the expression levels of cytokine proteins in the supernatant of MH-S and MLE12 cells, enzyme-linked immunosorbent assay (ELISA), a standardized biochemical analysis method, was used.

[0101] Sample preparation: The collected cell supernatant sample was processed appropriately at 4°C, 3000g, for 5 minutes to obtain the supernatant sample.

[0102] The specific experimental procedures are the same as in 1.5 of Example 1.

[0103] like Figures 19 to 23 The results showed that the expression of TNF-α, IL-6, and IL-1β in the MH-S and MLE12 cell adenosine treatment groups was significantly lower than that in the disease group and the disease plus group.

[0104] Any aspects of this invention not described in detail are well-known to those skilled in the art.

[0105] The preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. Use of adenosine in the preparation or prevention of a medicament for chronic obstructive pulmonary disease.

2. Use according to claim 1, characterized in that: The chronic obstructive pulmonary disease refers to acute exacerbation of chronic obstructive pulmonary disease.

3. Use according to claim 2, wherein: The acute exacerbation of chronic obstructive pulmonary disease is caused by Streptococcus pneumoniae.

4. The use according to claim 1, characterized in that: The medicament is a medicament for inhibiting cell activation and proinflammatory factor release through A2AR receptor.

5. The use according to claim 1, characterized in that: The adenosine is a compound in which N-9 of adenine is connected with C-1 of D-ribose through a β glycosidic bond.

6. Use according to any one of claims 1 to 5, characterized in that: The dose of the adenosine in animal experiments is 1-10 mg / kg.

7. Use according to any one of claims 1 to 5, characterized in that: The drug concentration of the adenosine in in vitro cell experiments is 1-10 uM.

8. Use according to any one of claims 1 to 5, characterized in that: The dosage form of the medicament is any one of tablet, capsule, granule, powder or liquid preparation.

Images