白介素-6受体拮抗剂对类风湿关节炎患者外周血单个核细胞Th17分化的影响  

The influence of interleukin-6 receptor antagonist to differentiation of Th17 peripheral blood mononuclear cells in patients with rheumatoid arthritis

作　　者：史群[1] 尤欣[1] 郑乐婷[1] 李梦涛[1] 张奉春[1] 赵岩[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科,北京100032

出　　处：《中日友好医院学报》2013年第3期159-163,F0002,共6页Journal of China-Japan Friendship Hospital

基　　金：国家自然科学基金面上项目资助(30872333和81072404);2010年杨森科学研究基金;北京协和医院青年基金资助

摘　　要：目的:研究重组人源化抗人白介素-6(IL-6)受体单克隆抗体——托珠单抗(TCZ)治疗类风湿关节炎(RA)的作用机制。方法:以8例长期接受甲氨蝶呤治疗的活动性RA患者为试验对象,每4周静脉滴注1次TCZ 8mg/kg,分别于治疗基线(W0)、治疗12周(W12)采集外周血,分离血清及提取外周血单个核细胞(PBMC)。结果:TCZ抑制RA患者PBMC的IL-17+CD4+T细胞(Th17)细胞分化,治疗12周时Th17细胞比例较治疗前明显下降。血清IL-17的水平12周时较治疗前显著下降(6.33±2.45pg/ml vs 11.3±5.73pg/ml,P<0.05);血清IL-6的水平12周时较治疗前显著下降(13.23±10.68pg/ml vs 48.07±22.37pg/ml,P<0.01)。并且TCZ治疗显著降低RA患者疾病活动性相关的DAS28、类风湿因子和C反应蛋白水平。结论:TCZ可能通过减少IL-6产生,抑制RA患者Th17细胞的分化,降低促炎症因子IL-17的产生,显著改善RA的疾病活动性,从而有效治疗RA。Objective：To investigate the mechanism of interleukin （IL）-6 receptor monoclonal antibody- tocilizumab（TCZ）on the therapy of rheumatoid arthritis（RA）.Methods：Eight patients with active RA were re- cruited and given intravenously TCZ at a dose of 8 mg/kg every 4 weeks.Peripheral blood was drawn at baseline（W0）and 12 weeks after the beginning of treatment（W12）.Serum was separated and peripheral blood mononuclear cells（PBMC）were extracted.Results：TCZ inhibited the differentiation of T helper cell（Th）-17.The percentage of IL-17＋CD4CF cells at W12 was reduced compared with that at W0.The level of IL-17 significantly decreased（6.33±2.45pg/ml vs 11.3±5.73pg/ml）after 12 weeks＇ treatment （P〈0.05）.There was a significant difference of IL-6 level between W12 （6.33±2.45pg/ml）and W0（11.3±5.73pg/ml）（P〈0.05）.In addition,RA related index including rheumatoid factor and C reactive protein was significandy improved after TCZ administration as well as disease activity score in 28 joints （DAS28）.Concluslon：TCZ nay efficaciously treat RA through the block of IL-6,and there after inhibiting the differentiation of Thl7 and production of IL-17.

关 键 词：类风湿关节炎 T辅助细胞-17 白介素-6 

分 类 号：R593.22[医药卫生—内科学]