Burkhardt H, Kalden J R
Department of Internal Medicine III, University of Erlangen-Nürnberg, Germany.
Rheumatol Int. 1997;17(3):85-90. doi: 10.1007/s002960050014.
An unprecedented arsenal of new xenobiotic immunosuppressive agents has been developed recently. Most of the new immunosuppressants have been tested primarily in the treatment of allograft rejection in experimental models of transplantation, and some of the new drugs have already proven their safety and efficiency in extensive clinical trials on transplant patients. Another field for their potential application is the treatment of autoimmune diseases. This review will give an overview of the therapeutic potential of the new xenobiotic drugs in different animal models of rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, multiple sclerosis, diabetes mellitus, thyroiditis and uveoretinitis. The new xenobiotics are either inhibitors of the de novo synthesis of nucleotides, for example mycophenolate mofetil, mizoribine, leflunomide, and brequinar, or are immunophilin-binding agents (cyclosporin, FK506 and rapamycin) that inhibit signal transduction and cell cycle progression in lymphocytes. A different mode of action is likely to account for the immunosuppressive effects of deoxyspergualin, which may interfere with intracellular chaperoning by the heat shock protein HSP70 and the activation of transcription factor NF-kappa B.
最近已开发出一系列前所未有的新型外源性免疫抑制剂。大多数新型免疫抑制剂主要在移植实验模型中用于治疗同种异体移植排斥反应，并且一些新药已在针对移植患者的广泛临床试验中证明了其安全性和有效性。它们潜在应用的另一个领域是自身免疫性疾病的治疗。本综述将概述新型外源性药物在类风湿性关节炎、系统性红斑狼疮、重症肌无力、多发性硬化症、糖尿病、甲状腺炎和葡萄膜视网膜炎等不同动物模型中的治疗潜力。新型外源性药物要么是核苷酸从头合成的抑制剂，例如霉酚酸酯、咪唑立宾、来氟米特和布喹那，要么是免疫亲和素结合剂（环孢素、FK506和雷帕霉素），它们抑制淋巴细胞中的信号转导和细胞周期进程。脱氧精胍菌素的免疫抑制作用可能是由不同的作用方式引起的，它可能会干扰热休克蛋白HSP70介导的细胞内伴侣蛋白功能以及转录因子NF-κB的激活。
