Maini R N, Brennan F M, Williams R, Chu C Q, Cope A P, Gibbons D, Elliott M, Feldmann M
Clinical Immunology Division, Kennedy Institute of Rheumatology, London, UK.
Clin Exp Rheumatol. 1993 Mar-Apr;11 Suppl 8:S173-5.
Our work has shown that TNF alpha is produced by cultured mononuclear cells from rheumatoid arthritis joints and appears to regulate the production of IL-1. Immunohistochemical examination has shown the presence of TNF alpha in the synovium, e.g. in the lining layer, some endothelial cells and most importantly, in the cells in the cartilage pannus junction. TNF receptors (both p55 and p75) have a similar distribution, thereby suggesting that TNF has the potential for autocrine and paracrine activity in the joint. The concept that TNF alpha is pathogenic in inflammatory arthritis has been validated by showing that neutralizing monoclonal anti-TNF antibodies significantly attenuate collagen-induced arthritis in mice. In preliminary trials in rheumatoid patients anti-TNF appears to have an impressive effect on indices of disease activity including C-reactive production and serum amyloid-A production. TNF alpha appears to be a relevant therapeutic target in rheumatoid disease.
我们的研究表明，肿瘤坏死因子α（TNFα）由类风湿性关节炎关节培养的单核细胞产生，且似乎可调节白细胞介素-1（IL-1）的产生。免疫组织化学检查显示，滑膜中存在TNFα，如在衬里层、一些内皮细胞中，最重要的是，在软骨血管翳交界处的细胞中。肿瘤坏死因子受体（p55和p75）有类似的分布，从而表明TNF在关节中具有自分泌和旁分泌活性的潜力。通过证明中和性抗TNF单克隆抗体可显著减轻小鼠胶原诱导的关节炎，TNFα在炎性关节炎中具有致病性这一概念得到了验证。在类风湿患者的初步试验中，抗TNF似乎对包括C反应蛋白产生和血清淀粉样蛋白A产生在内的疾病活动指标有显著效果。TNFα似乎是类风湿疾病中一个相关的治疗靶点。
