摘要
目的研究霉酚酸(mycophenolicacid,MPA)对系统性红斑狼疮(systemiclupuserythematosus,SLE)患者外周血单个核细胞(PBMCs)细胞因子分泌及Th细胞亚群的作用。方法分离SLE患者及健康对照的外周血单个核细胞(PBMCs),加入MPA或对照药物地塞米松(DEX)培养48h,用ELISA法测培养上清中IL-10、IL-12及IFN-γ的水平,用三色流式细胞术检测培养细胞中CD4+IFN-γ+IL-10-T细胞、CD4+IFN-γ-IL-10+T细胞及CD4+IFN-γ+IL-10+T细胞百分率。结果①MPA可使SLE患者PBMCs培养上清中IL-10、IL-12及IFN-γ的分泌显著降低,而DEX却使IL-10分泌水平增高。②MPA可降低SLE患者培养的PBMCs中CD4+IFN-γ+IL-10-T、CD4+IFN-γ-IL-10+T及CD4+IFN-γ+IL-10+T细胞比率,而DEX在使CD4+IFN-γ+IL-10+T细胞亚群比率增高的同时,却使CD4+IFN-γ+IL-10-T细胞亚群的比率降低。结论MPA可抑制SLE患者PBMCs细胞因子分泌,并降低SLE患者外周血培养的PBMCs中Th亚群比率。
Objective To investigate the effects of mycophenolic acid （MPA） on production of cytokines and Th subsets in the peripheral blood mononuclear cells （PBMCs） from patients with systemic lupus erythematosus （SLE） at both cellular and molecular level. Methods PBMCs prepared from both SLE patients and healthy controls were cultured with MPA, or DEX as a control. ABC-ELISA method was utilized to measure the levels of IL-10, IL-12, and IFN-γ in the supernatants of cultured PBMCs from SLE, and three-color cytometry was applied to detect the percentage of CD4^＋ IFN-γ^＋ IL-10^-, CD4^＋ IFN-γ^- IL-10^＋, and CD4^＋ IFN-γ^＋ IL-10^＋ T subsets of lymphoeytes. Results The levels of IL-10, IL-12, and IFN-γ were all significantly elevated in the supernatants of cultured PBMCs from SLE, compared with normal control. The production of IL-10, IL-12, and IFN-γ by PBMCs from SLE both spontaneously and under the stimulation of phytohaemagglutinin （PHA） was significantly reduced by MPA, while the secretion of IL-10 was enhanced by DEX. The pereentages of CD4^＋ IFN-γ^- IL-10^＋ and CD4^＋ IFN-γ^＋ IL-10^＋ T subsets in cultured PBMCs from SLE were significantly increased and MPA could decrease the percentages of all three subsets. In contrast, DEX increased the pereentage of CD4^＋ IFN-γ^＋ IL-10^＋ T subset and decreased the percentage of CD4^＋ IFN-γ^＋ IL-10^- T subset. Conclusion The beneficial effect of MPA on SLE may be due to the inhibition of MPA on the abnormal production of IL-10, IL-12, and IFN-γ and on the activation and proliferation of CD4^＋ IFN-γ^＋ IL-10^-, CD4^＋ IFN-γ^- IL-10^＋, and CD4^＋ IFN-γ^＋ IL-10^＋ T subsets, while DEX exhibits both similar and different effects, indicating a complementary function of these two drugs in clinical treatment of SLE.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2006年第5期555-558,共4页
Immunological Journal
基金
江苏社会发展基金资助项目(BS2001048)
