TNF alpha as a therapeutic target in rheumatoid arthritis.

Circulatory shock Pub Date : 1994-08-01
M Feldmann, F M Brennan, M Elliott, P Katsikis, R N Maini
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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease with inflammatory manifestations in the peripheral synovial joints, which are infiltrated by activated T cells, macrophages, and plasma cells. We have investigated the role of cytokines in RA and have proposed that tumour necrosis factor has a pivotal role in the pathogenesis of this disease. This chapter describes those studies, which led to the first clinical trial in RA patients using a chimeric anti TNF alpha antibody. In addition to pro-inflammatory cytokine production, at sites of inflammation such as the RA synovial joint, there is also evidence for homeostatic immunoregulatory mechanisms which include the production of cytokine inhibitors, such as soluble TNF-R and the IL-1 receptor antagonist, and cytokines with immunoregulatory properties like IL-10. The evidence for these inhibitors in RA is presented, and the relevance of this homeostatic mechanism in relation to chronic inflammatory diseases is discussed.

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TNF α作为类风湿关节炎的治疗靶点。
类风湿性关节炎(RA)是一种自身免疫性疾病,以滑膜周围关节炎症为表现,被活化的T细胞、巨噬细胞和浆细胞浸润。我们研究了细胞因子在类风湿性关节炎中的作用,并提出肿瘤坏死因子在这种疾病的发病机制中起关键作用。本章描述了这些研究,这些研究导致了首次在RA患者中使用嵌合抗TNF α抗体的临床试验。除了促炎细胞因子的产生,在炎症部位,如RA滑膜关节,也有证据表明稳态免疫调节机制包括细胞因子抑制剂的产生,如可溶性TNF-R和IL-1受体拮抗剂,以及具有免疫调节特性的细胞因子,如IL-10。这些抑制剂在类风湿性关节炎中的证据被提出,并讨论了与慢性炎症疾病相关的这种体内平衡机制的相关性。
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