系统性红斑狼疮患者IL-10、IFN-γ、IP-10和IL-12的异常表达及环孢素A和环磷酰胺对其的影响

The abnormal expression of IL-10, IFN-γ, IP-10 and IL-12 in patients with systemic lupus erythematosus and the effects of cyclosporine A and cyclophosphamide on it

目的:探讨系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMCs)的干扰素(IFN)-γ、白细胞介素(IL)-10、干扰素-γ诱生蛋白(IP)-10和IL-12的表达水平及环孢素A(CsA)和环磷酰胺(CY)对其的影响。方法:应用酶联免疫吸附法检测血清及PBMCs培养上清上述细胞因子水平;运用流式细胞术检测CD4+T细胞中分泌IFN-γ和分泌IL-10的细胞百分率。结果:SLE患者血清及PBMCs培养中IFN-γ、IL-10、IL-12和IP-10水平增高,PBMCs中表达IL-10的CD4+T细胞比例明显增高(P<0.05),表达IFN-γ的CD4+T细胞的比例亦有所增高;CsA及CY均能抑制SLEPBMCs培养中IL-10水平,并对PHA刺激下的IFN-γ、IP-10和IL-12分泌增高有抑制作用,且CsA的抑制作用更为显著;CsA和CY还能抑制PBMCs中表达IFN-γ及表达IL-10的CD4+T细胞的比例增高,且CsA的抑制幅度更大。结论:SLE患者体内存在细胞因子网络失调。CsA与CY均能干扰SLE的细胞因子网络失调的免疫病理过程,且CsA的调节作用更为显著。

Objective： To investage the expression of IL-10, IL-12, IFN-γ, IFN-γ-inducible protein （IP） -10 by peripheral blood mononuclear cells （PBMCs） in patients with systemic lupus erythematosus （SLE） and the effects of cyclosporine A （CsA） and cyclophosphamide （CY） on it. Methods： The cultured PBMCs from SLE patients and health control were treated with CsA or CY. We measured serum levels of IL-10, IL-12, IFN-γ and IP-10 as well as spontaneous and PHA-stimulated production of these cytokines by PBMCs both in controls and in patients with SLE by ABC-ELISA .Meantime, flow cytometry was applied to analyse the percentage of CD4^＋ IFN-γ and CD4^＋ IL-10^＋ T subsets. Results：The levels of IL-10, IL-12, IFN-γ and IP -10 of the serum as well as the PBMC cultures supernatants increased in SLE patients. The percentages of both IL-10-producing and INF-γ-producing CD4^＋T subsets also increased markedly. CsA and CY suppressed the increased production of IL-IO by patients＇PBMCs, And also inhibited the increased productions of IL-12,IFN-γand IP-10 induced by PHA-stimulating. Moreover, CsA and CY decreased the percentages of both IFN-γ-producing and IL-10-producing CD4^＋T cells in SLE patients. CsA showed a more significant effect. Conclusion： Abnormally high production of IL-10,IFN-γ,IP-10 and IL-12 and the increase of both IL-lO-producing and IFN-γ-producing T cells existed in patients with SLE. CSA and CY disturbed the pathogenic process related to SLE above. Furthermore, CsA was more effective in inhibiting the pathogenic process of SLE.