Effect Of Inhaled Cyclosporin A On Airway Inflammation And CD4~+CD25~+IL-10~+T Cells In Asthmatic Mouse

Background and Purpose:Bronchial asthma,also named asthma,is a common disease which becomes a severe hazard to public health,affected worldwide.As a result of the unknown etiology and complex mechanism,the therapy of asthma is still an intractable problem.Although inhaled glucocorticoids(GCs) are very effective for the treatment of most patients with asthma,an important subgroup of patients require oral GCs to control their disease at the risk of considerable side effects.The recent disturbing increase in the prevalence of asthma in the developed world has major health and economic consequences.Thus,it is imperative that we should look for a breakthrough in the asthmatic treatment.The central role of Th2-cell-derived cytokines indicates that strategies to cure or provide long-term relief from asthma symptoms need to target this allergen-specific Th2 response.The patients of asthma usually have an impair function of regulatory T cells(Tregs) and a low level of IL-10.allergen-induced cytokine production by allergen-specific Th2 cells was inhibited by allergen-induced IL-10-secreting Tregs in an IL-10-dependent manner.an alternative and more attractive strategy is the local delivery of inhibitory signals through the induction of allergen-activated IL-10-secreting Tregs.Induction of antigen-specific IL-10-secreting Tregs is an appealing future therapeutic area for asthma.IL-10 plays an essential role in the functional activities of IL-10-secreting Tregs and in the regulation of Th2 responses and allergic responses.The anti-inflammatory and immunological properties of IL-10 make it an attractive cytokine for the control of asthmatic responses.Several immunomodulatory regimens and calcium channels blocker have been shown to increase IL-10 synthesis.Induction of IL-10 synthesis may contribute to the clinical efficacy of GCs therapy in asthma since patients who fail to respond clinically to GCs also fail to respond ex vivo to GCs for induction of IL-10 synthesis.it might be possible to harness these effects to promote the induction of antigen-specific IL-10- secreting Tregs,either by treatment with GCs alone or together with other drugs,induction of IL-10 synthesis is associated with amelioration of disease symptoms.Cyclosporine A(CsA) is a well-known immunosuppressant that blocks NF-AT translocation into the nucleus by inhibition calcineurin phosphatease activity.It was proved that can inhibit airway inflammation and decrease the dosage of GCs,but the mechanism of its anti-inflammatory function is still unclear.The purpose of our study is to observe the influence of CsA on the level of IL-10,IL-4,IL-5,IL-2,IFN-γand inflammatory cells in ovalbumin(OVA) -induced mouse model and detect the relationship between IL-10 and CD4~+CD25~+IL-10~+T cells,consequently,investigate the mechanism of resolution in asthmatic inflammation and provide the oretical basis for the clinical therapy and development of new drugs in asthma.Material and methods:BALB/c mice(n=40) were divide into four groups:control group,model group,CsA group and CsA +anti-IL-10 antibody group(n=40).Mice were sensitized to OVA by intraperitoneal injection and challenged with OVA aerosol for 7 consecutive days.The concentration of cytokines including IL-4,IL-5,IL-2,IL-10 and IFN-γin BALF were measured by using ELISA Kits.Lung tissue sections were stained with hematoxylin-eosin(HE) and Alcian blue /periodic acid Schiff(AB/PAS) to observe general morphology and goblet cells.Flow cytometry were used to detect the percentage of CD4~+CD25~+IL-10~+T cells. Results:Treated by CsA aerosol significantly reduced the numbers of inflammatory cells and the level of IL-4JL-5 and IL-2,also,resolved pulmonary infiltration of inflammatory and goblet cells hyperplasia,with a high level of IL-10 in BALF (p<0.01).Further,the percentage of CD4~+CD25~+IL-10~+T cells presented negative correlations with the numbers of inflammatory cells,goblet cells hyperplasia and the levels of Th2 cytokines(p<0.01).Conclusions:1.CsA can inhibit airway inflammation in asthmatic mouse,as a result of the up-regulation in the level of IL-10 probably.CD4+CD25+IL-10+T cells may play an important role during the process.2.CsA-induced increase of CD4~+CD25~+IL-10~+ T cells to up-regulate the level of IL-10 may provide theoretical basis and practical value.