The Mechanism Of Interleukin-33 In Chronic Obstructive Pulmonary Disease

Background Chronic Obstructive Pulmonary Disease(COPD)is a common and frequently respiratory disease that causes severe harm to human health.This disease is closely related to smoking and air pollution.The mechanism of COPD is a chronic inflammatory response released by inflammatory cells such as neutrophils,macrophages and lymphocytes,through various inflammatory factors.Interleukin 33(IL-33)is a newly discovered inflammatory regulator in recent years,and proved to be a member of IL-1 family.It is widely expressed in various tissues of mammals,especially in the mucous membrane system(such as respiratory mucosa),brain and spinal cord,and so on.The main cells that mediate IL-33 secretion are Smooth muscle cells,fibroblasts,epithelial and endothelial cells,as well as some immune cells,such as dendritic cells,macrophages and mast cells.ST2 is a membrane receptor of IL-33,the former is widely expressed in a variety of immune cells.When IL-33 and ST2 combine,it can induce a variety of cytokines,such as IL-2,IL-4,IL-5,IL-6,IL-8,IL-13,IFN-?,TNF-?.Then,this is one of the key factors involved in TH2-mediated inflammatory response.The current research in the allergic asthma mouse model showed that the combination of high expression of IL-33 and ST2 promoted the expression of lung fibroblastsand inflammatory cells,which aggravated inflammation in asthma.Furthmore,while the use of its receptor antagonists could reduce the production of Th2 cytokines and alleviate inflammation in asthma.This suggests that IL-33 may play a strong role in the intervention of respiratory diseases.However,literature review shows that it is not clear about the role and mechanism of IL-33 in COPD.Therefore,this study will discuss the role and possible mechanism of IL-33 in COPD from clinical patients and animal experiments respectively.Objective To explore the role of IL-33 in COPD and its possible mechanism.It may provide new theoretical basis and research direction for future prevention and treatment.Methods Part one(Clinical observation): Plasma and relevant clinical data were collected from 20 patients with COPD(case group)and20 healthy people(control group)in our hospital.(1)IL-33,IL-6,IL-8and TNF-?concentration in plasma were detected by ELISA,and the differences between the two groups were compared.(2)The correlation between IL-33 expression level and patients' lung function,FEV1/FVC,white blood cell count and neutrophil count was analyzed.Part two(Animal experiments): SD rats were randomly divided into the normal control group,COPD group,and IL-33 nasal drip group with 5 rats each.(1)HE staining in lung tissue.(2)The expression level of IL-33 in lung tissue was detected by immunohistochemistry.(3)Plasma was collectedand separated,and IL-33,IL-6,IL-8 and TNF-?concentration in the plasma of the three groups were detected by ELISA.(4)Protein was extracted from lung tissue and the expression levels of IL-33,IL-6,IL-8and TNF-?were detected by ELISA.Results: Part one(Clinical observation):(1)There were no significant differences in age,gender and body mass index between the case group and the control group.(2)Detected by ELISA,the expression levels of IL-33,IL-6,IL-8 and TNF-? in the plasma were significantly higher in the case group than in the control group,which were 313.45±27.44 vs 165.15 ± 8.05,22.00±3.88 vs 5.95±2.16,161.70±14.31vs40.70±6.30,73.90±11.76 vs 40.70±6.30,respectively.(3)Spearman correlation was used to analyze the relationship between IL-33 and other inflammatory indicators.The study showed that IL-33 was highly correlated with the leukocytes,FEV1/FVC,IL-6,IL-8 and TNF-?,with correlation coefficients of 0.879,0.850,0.972,0.983,0.977,respectively.Part two(Animal experiments):(1)Pathological sections showed that in IL-33 group,bronchial wall thickened,mucosal hyperplasia,epithelial cells were seriously exfoliated,alveoli were significantly dilated,alveolar septa were narrowed and ruptured,adjacent alveoli fused into larger cystic Spaces,and a large number of lymphocytes and plasma cells were infiltrated in the interstation.(2)Immunohistochemical detection of IL-33 expression sites in lung tissues showed that IL-33 was expressed inmacrophages in both COPD group and IL-33 group,and the expression level in COPD group was higher than that in IL-33 group.(3)According detected the concentrations of IL-33,IL-6,IL-8 and TNF-? in plasma among the control group,IL-33 group and COPD group by ELISA,it shows that 11.64±2.06 vs 37.74±2.98 vs 150.98±2.85,16.61±1.91 vs39.79±0.84 vs 76.04±1.69,185.79±9.60 vs 420.12±7.42 vs 762.77±16.59,39.92±4.84 vs 105.22±5.73 vs 200.55±7.43,respectively.According to the comparison of multiple groups,there were statistically significant differences among the three groups.(4)According detected the concentrations of IL-33,IL-6,IL-8 and TNF-? in lung tissue among the control group,IL-33 group and COPD group by ELISA,it shows that37.28±6.24 vs 79.29±6.07 vs 219.20±3.26,30.67±1.93 vs 78.25±3.67 vs138.26±5.48,216.93±6.76 vs 511.97±6.66 vs 510.74±2.21,81.16±6.80 vs185.70±6.27 vs 319.10±7.20,respectively.According to the comparison of multiple groups,there were statistically significant differences among the three groups.Conclusion(1)IL-33 is involved in the occurrence and development of COPD;(2)IL-33 mediates inflammation in COPD,which may regulate inflammatory response and promote the release of inflammatory mediators.(3)In the COPD model,IL-33 is mainly expressed in alveolar macrophages,and it is speculated that IL-33 is the key mechanism to regulate macrophages.