Immunosuppression in organ transplantation.

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.