Anti-TNFα therapy is useful in rheumatoid arthritis and Crohn's disease:: Analysis of the mechanism of action predicts utility in other diseases
Anti-TNFα therapy is useful in rheumatoid arthritis and Crohn's disease:: Analysis of the mechanism of action predicts utility in other diseases
复制标题
DOI：
10.1016/s0041-1345(98)01365-7
复制
发表时间：
1998-12-01
影响因子：
0.9
通讯作者：
Maini, RN
中科院分区：
文献类型：
--
作者：
Feldman, M;Taylor, P;Maini, RN
虽然研究疾病动物模型的发病机制并不困难，但对人类疾病发病机制的分析存在多重约束，导致了有趣的两难境地，例如我们在疾病中可以在多大程度上依赖和推断动物模型？20世纪80年代末，我们在体外和体内研究了细胞因子在类风湿滑膜中的表达和调节，发现肿瘤坏死因子α在类风湿滑膜中起着重要作用，因为它调节另一种炎性细胞因子白介素1的表达。1我们认为阻断肿瘤坏死因子α将在炎症过程中发挥重要作用，因此在临床上是有用的。这一预测已经在我们领导的临床试验中得到证实，这些试验使用的是Centocor的嵌合单抗CA2，现在被称为Remicaide。使用Celltech3产生的人源化抗体和免疫公司产生的名为Enbrel的肿瘤坏死因子受体p75 IgGFc融合蛋白也报告了阳性结果。4近期对抗肿瘤坏死因子α的临床疗效进行了综述。5.
WHILE it is not to difficult to study the pathogenesis of animal models of disease, there are multiple constraints on analyses of the pathogenesis of human disease, leading to interesting dilemmas such as how much can we rely on and extrapolate from animal models in disease? In the late 1980s, as a result of investigating cytokine expression and regulation in rheumatoid synovium, both in vitro and in vivo, we found that tumor necrosis factor (TNF) α was of major importance, as it regulated the expression of the other proinffammatory cytokine interleukin-1 (IL-1). 1 We proposed that blocking TNFα would thus have major effects on the inffammatory process and hence would be clinically useful. 2 That prediction has been substantiated in clinical trials that we have led using Centocor’s chimaeric monoclonal antibody, cA2, now termed Remicaide. Positive results were also reported using a humanized antibody produced by Celltech3 and also using a TNF-receptor p75 IgGFc fusion protein, produced by Immunex, termed Enbrel. 4 Clinical effects of anti-TNFα have recently been reviewed. 5