Fox D A
Specialized Center of Research in Rheumatoid Arthritis, University of Michigan Medical Center, Ann Arbor 48109-0358, USA.
Am J Med. 1995 Jul;99(1):82-8. doi: 10.1016/s0002-9343(99)80109-0.
Biological therapies for rheumatoid arthritis (RA) make use of molecules (including derivative and recombinant forms) produced by cells of the immune system or by cells that participate in inflammatory reactions. Development of monoclonal antibodies against cell-surface structures that are lineage or subset specific has led to trials of anti-T-cell reagents in RA, but results thus far must be regarded as a significant therapeutic disappointment. A monoclonal antibody designed to interfere with the action of a cytokine, tumor necrosis factor alpha (TNF-alpha), has been studied in both open and controlled trials. Treatment with this antibody resulted in marked changes in indices of inflammation, but duration of responses may be limited by the eventual development of antibodies to the anti-TNF-alpha antibody. Immunomodulatory strategies that use the immune system to regulate autoimmune activity have been developed based on animal studies, and evaluation of oral collagen as a treatment in RA is currently underway. If successful, this approach would represent a new direction in the treatment of human autoimmune disease. In the future, use of gene therapy directed to the joint could be a powerful approach to treatment of RA. Rational use of biological therapies in RA will depend, in part, on improved understanding of the pathogenesis of this condition.
类风湿关节炎（RA）的生物疗法利用免疫系统细胞或参与炎症反应的细胞产生的分子（包括衍生物和重组形式）。针对谱系或亚群特异性的细胞表面结构开发单克隆抗体，已引发了抗T细胞试剂在RA中的试验，但迄今为止的结果必须被视为重大的治疗失望。一种旨在干扰细胞因子肿瘤坏死因子α（TNF-α）作用的单克隆抗体，已在开放试验和对照试验中进行了研究。用这种抗体治疗导致炎症指标发生显著变化，但反应持续时间可能会受到最终产生抗TNF-α抗体的限制。基于动物研究开发了利用免疫系统调节自身免疫活性的免疫调节策略，目前正在对口服胶原蛋白作为RA治疗方法进行评估。如果成功，这种方法将代表人类自身免疫性疾病治疗的新方向。未来，针对关节的基因治疗的应用可能是治疗RA的有力方法。在RA中合理使用生物疗法将部分取决于对这种疾病发病机制的更好理解。
