The Effects Of CD4~+T Cells And Cytokines In The Pathogenesis And Immunotherapy Of Myasthenia Gravis

Objective:To evaluate the cytokines of CD4~+ T cells in patients with myasthenia gravis(MG) and investigate the influences of Immunotherapy on the cytokines. Methods:First part:We tested the cytokines(IL-2,IL-12,IFN-γ,TNF-α,IL-4,IL-10, IL-13 and IL-17) of serum in 93 patients with MG and 34 healthy controls in Huashan Hospital.Datas were analyzed by unpaired t test in case of Gaussian distribution, while the nonparametric test was applied in case of abnormal distribution.Second part:We measured the cytokines of patients before and after different kinds of immunotherapy,such as corticosteroids,intravenous methylprednisolone pulse, intravenous immunoglobulin and tacrolimus.Then the results were analyzed by paired t test.Result:Compared with healthy controls,the cytokines associated with Th1 cells(IL-2,IL-12,IFN-γand TNF-α) were all fairly increased.For the cytokines secreted by Th2 cells,IL-4 and IL-10 were similar to the controls while IL-13 was increased.The IL-17 secreted by Th17 cells was comparable with controls. The cytokoines of ocular MG and generalized MG patients were comparable,and so were patients with different course of disease.IL-12 and IL-13 in patients treated with corticosteroids decreased while IL-4 increased after the treatment.IFN-γdecreased after treatment of intravenous methylprednisolone pulse.IL-13 and IL-17 in patients treated with intravenous immunoglobulin decreased after treatment.However,no marked changes were observed after treatment of tacrolimus.Conclusion:Th1 cytokines play important roles in pathogenesis of MG, while Th2 cytokines have complex and contrasting roles.Function of Th17 and IL-17 is unclear,which might be covered by active Th1 system.Clinical pattern and severity are not associated with cytokines level,which shows effects of other factors. Relationship between course of disease and level of cytokines is not found,which suggests a process of activating-lowering in immune system and may be relevant to immunotherapy.Small sample researchs on different kinds of immunotherapy indicate different therapeutic mechanisms initially.Corticosteroids inhibits Th1 and Th2 cells,and the increase of IL-4 is protective in MG.Intravenous methylprednisolone pulse decreases IFN-γand suppresses activation of mononuclear macrophage.Intravenous immunoglobulin plays its role through down-regulation of IL-17.Tacrolimus inhibits T cells by cytokine network and enhances Treg cells, but it did not observed in this study.