Feldmann M, Brennan F M, Elliott M, Katsikis P, Maini R N
Mathilda and Terence Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
Circ Shock. 1994 Aug;43(4):179-84.
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.
类风湿关节炎（RA）是一种自身免疫性疾病，在外周滑膜关节出现炎症表现，这些关节被活化的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关节炎中的作用，并提出肿瘤坏死因子在该疾病的发病机制中起关键作用。本章描述了那些研究，这些研究促成了类风湿关节炎患者使用嵌合抗TNFα抗体的首个临床试验。除了在炎症部位如类风湿关节炎滑膜关节产生促炎细胞因子外，也有证据表明存在稳态免疫调节机制，其中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。文中介绍了类风湿关节炎中这些抑制剂的证据，并讨论了这种稳态机制与慢性炎症性疾病的相关性。
