Oka T, Yoshimura N
Second Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Jpn J Pharmacol. 1996 Jun;71(2):89-100. doi: 10.1254/jjp.71.89.
The immunological barrier remains the major obstacle to the widespread use of transplantation as a replacement therapy for terminal organ failure. Since the first successful renal transplant, performed by Hume et al. (1952), there has been an elusive search for agents that can render the immune mechanism unresponsive to the specific alloantigen stimulus of the engrafted organ, while sparing non-specific host resistance. Immunosuppressive therapies in organ transplantation can be divided into the following four main classes: chemical (pharmaceutical), biological (immunological), physical (radiological) and surgical. Of these, chemical agents (drugs) have continued to play a principal role. The discovery of new immunosuppressive drugs such as corticosteroids, ciclosporin, azathioprine and FK506 have been epoch-making discoveries at each stage in the history of clinical organ transplantation. The recent immunosuppressants were designed to focus their action selectively on T and/or B cells by inhibiting cytokine synthesis (ciclosporin, FK506), cytokine action (rapamycin), or cell differentiation (15-deoxyspergualin) pathways, rather than to act on immune systems in a non-selective fashion. At the present time, however, there is no single panacea. To achieve the maximum preventive and therapeutic effects with the minimum toxicity, two or more immunosuppressive drugs are used appropriately in combination, taking the mechanisms of action of each into consideration.
免疫屏障仍然是移植作为终末期器官衰竭替代疗法广泛应用的主要障碍。自休姆等人（1952年）首次成功进行肾移植以来，人们一直在寻找能使免疫机制对移植器官的特异性同种异体抗原刺激无反应，同时又不影响非特异性宿主抵抗力的药物。器官移植中的免疫抑制疗法可分为以下四大类：化学（药物）、生物（免疫）、物理（放射）和手术。其中，化学药物一直发挥着主要作用。新免疫抑制药物如皮质类固醇、环孢素、硫唑嘌呤和FK506的发现，在临床器官移植历史的每个阶段都是具有划时代意义的发现。最近的免疫抑制剂旨在通过抑制细胞因子合成（环孢素、FK506）、细胞因子作用（雷帕霉素）或细胞分化（15-脱氧精胍菌素）途径，选择性地将其作用集中于T细胞和/或B细胞，而不是以非选择性方式作用于免疫系统。然而，目前还没有一种万灵药。为了以最小的毒性实现最大的预防和治疗效果，需要考虑每种药物的作用机制，适当联合使用两种或更多种免疫抑制药物。
