Feldmann M, Brennan F M, Williams R O, Elliott M J, Maini R N
Kennedy Institute of Rheumatology, Sunley Division, Hammersmith, London, U.K.
J Inflamm. 1995;47(1-2):90-6.
The cloning of cytokine cDNAs has permitted the analysis of cytokine expression in diseased sites such as rheumatoid joints. A very wide range of cytokines were detected, mostly with proinflammatory activities. From the analysis of cytokine regulation in rheumatoid joint cell cultures using neutralizing anti-cytokine antibodies, it was found that blockade of TNF alpha reduced the production of other proinflammatory cytokines. Hence TNF alpha was a potential therapeutic target. This concept was tested successfully in collagen induced arthritis in mice and led to clinical trials of anti-TNF alpha antibody in rheumatoid arthritis (RA) in humans. The mechanism of action of anti-TNF alpha will be discussed.
细胞因子cDNA的克隆使得对诸如类风湿关节等患病部位的细胞因子表达进行分析成为可能。检测到了种类繁多的细胞因子，其中大多数具有促炎活性。通过使用中和性抗细胞因子抗体对类风湿关节细胞培养物中的细胞因子调节进行分析发现，阻断肿瘤坏死因子α（TNFα）可减少其他促炎细胞因子的产生。因此，TNFα是一个潜在的治疗靶点。这一概念在小鼠胶原诱导性关节炎中得到了成功验证，并促成了抗TNFα抗体在人类类风湿关节炎（RA）中的临床试验。本文将讨论抗TNFα的作用机制。
