【摘要】 目的探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白[rhTNFR:Fc,益赛普(etaner-cept)]治疗类风湿关节炎(RA)的免疫学机制,了解rhTNFR:Fc对RA患者血清中致炎及抗炎性细胞因子的作用,比较rhTNFR:Fc和甲氨蝶呤(MTX)对这些细胞因子作用的不同,为rhTNFR:Fc治疗RA提供进一步的实验依据。方法采用酶联免疫吸附试验(ELISA)检测RA患者rhTNFR:Fc治疗前后血清中白细胞介素(IL)-1"、IL-6、IL-10、肿瘤坏死因子(TNF)-!和干扰素(INF)-#浓度。观察rhTNFR:Fc对细胞因子的影响。结果&%RA患者血清中的炎性细胞因子TNF-!、INF-#、IL-1"、IL-6的水平均高于健康对照组,其中IL-6、INF-#、TNF-!的水平与健康对照组相比差异有统计学意义(P<0.01),抗炎性细胞因子IL-10的水平低于健康对照组,但两者相比差异无统计学意义(P>0.05)。&’rhTNFR:Fc治疗RA后血清中Th1型细胞因子TNF-!、INF-#、IL-1"、IL-6水平均明显降低(P<0.01),而Th2型细胞因子IL-10的水平明显提高(P<0.01)。&(RA患者血清中TNF-!水平与肿胀关节数及肿胀关节指数呈正相关(P<0.05)。&)对临床指标的分析表明,rhTNFR:Fc治疗RA疗效确切。结论rhTNFR:Fc可以降低RA患者血清中TNF-!、INF-#、IL-1"、IL-6的水平,同时升高IL-10水平;在抑制了Th1型细胞因子的同时,增强了Th2型细胞因子的效应,从而改善RA的病情。更多还原

【Abstract】 Objective To determine the effect of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR:Fc) treatment on the level of cytokines in rheumatoid arthritis (RA). Method Thirty patients with RA were treated with rhTNFR:Fc (25 mg, twice a week) as monotherapy. The pro-inflammatory cytokines such as TNF-α, INF-γ, IL-1β, IL-6 and anti-inflammatory cytokines such as IL-10 were measured in RA sera pre-and post-24 weeks of therapy. Results The level of inflammaory cytokines of RA such as IL-6, TNF-α, INF-γ were significantly higher than the healthy controls (P<0.01), respectively. The level of IL-1β was higher than the healthy controls, but had no significant difference between RA and control group (P>0.05). The level of TNF-α, INF-γ, IL-1β, IL-6 were significantly decreased after treated with rhTNFR:Fc (P<0.01). In contrast, IL-10 was remarkably increased (P<0.01). The pretreatment TNF-α level correlated to swollen joint counts and swollen joint index. Conclusion rhTNFR:Fc therapy may down-regulate the level of pro-inflammatory cytokines and up-regulate the level of anti-inflammatory cytokines, and there by decrease the Th1/Th2 cytokine ratio.更多还原