MacLeod A M, Thomson A W
Department of Medicine and Therapeutics and Immunopathology Laboratory, Medical School, University of Aberdeen, Scotland U.K.
Medicina (Firenze). 1990 Jul-Sep;10(3):329-32.
In this brief review, we outline the properties of the new macrolide immunosuppressant FK-506. This selective anti-T cell agent has a similar mode of action to cyclospirin A (CSA). It is, however, more powerful, has the capacity (unlike CSA) to reverse liver allograft rejection and appears to have a higher therapeutic index than CSA in patients receiving organ transplants. Preliminary data suggest that renal function is better in recipients of liver transplants given FK-506 as primary therapy compared with those given CSA. In addition, evidence has been presented that FK-506-treated patients have shorter hospital stay than those receiving treatment with CSA. Other factors require to be taken into account, but it may be that it will prove less expensive in the future to treat patients with FK-506 than with CSA. The potential of FK-506 for the control of autoimmune diseases has been demonstrated in rodent models of rheumatoid arthritis, type I diabetes, posterior uveitis, allergic encephalomyelitis and glomerulonephritis. In the clinical field, FK-506 has been used in two cases of nephrotic syndrome resulting from glomerulonephritis; there was improvement in proteinuria and no decline in renal function. Studies to date have been restricted to one clinical centre although many hundreds of organ graft recipients have been studied. Both longer term and multi-centre investigations are urgently required, but it appears that FK-506 may offer considerable potential as an immunotherapeutic agent.
在这篇简短的综述中,我们概述了新型大环内酯类免疫抑制剂FK-506的特性。这种选择性抗T细胞药物的作用模式与环孢素A(CSA)相似。然而,它的效力更强,具有(与CSA不同)逆转肝移植排斥反应的能力,并且在接受器官移植的患者中似乎比CSA具有更高的治疗指数。初步数据表明,与接受CSA治疗的患者相比,接受FK-506作为主要治疗的肝移植受者的肾功能更好。此外,有证据表明,接受FK-506治疗的患者住院时间比接受CSA治疗的患者短。其他因素也需要考虑,但未来用FK-506治疗患者可能比用CSA更便宜。在类风湿性关节炎、I型糖尿病、后葡萄膜炎、变应性脑脊髓炎和肾小球肾炎的啮齿动物模型中,已证明FK-506具有控制自身免疫性疾病的潜力。在临床领域,FK-506已用于两例由肾小球肾炎引起的肾病综合征;蛋白尿有所改善,肾功能没有下降。尽管已经对数百名器官移植受者进行了研究,但迄今为止的研究仅限于一个临床中心。迫切需要进行长期和多中心研究,但FK-506似乎作为一种免疫治疗药物具有相当大的潜力。