Recent advances in immunosuppression

Abstract

T THE PRESENT time, cyclosporin A (CsA) and FK506 (tacrolimus; Prograf, Fujisawa USA, Deerfield, IL) are both used as immunosuppressive agents in the transplant setting. The introduction of CsA to the clinical arena in the late 1970s heralded an increased success not only in solid organ transplantation, but also in bone marrow transplantation. However, chronic administration of CsA is not without potential and at times serious side effects including hypertension, neurologic toxicity, and nephrotoxicity. Isolated in 1984, FK506 is 10- to 100-fold more potent than CsA in inhibiting T cell function in vitro. However, its use is still accompanied by serious side effects including decreased renal function, glucose intolerance, and infectious and neurologic complications. Thus, efforts to develop new agents with less toxicity, but equal or improved immunosuppressive efficacy are ongoing. Rapamycin is a novel immunosuppressant whose use in clinical transplantation is beginning to be explored. Although structurally similar to FK506, rapamycin has a distinct mechanism of action. This article focuses on the mechanisms by which these drugs exert their biological effects. An understanding of the mechanisms involved in immunosuppression is helpful'in anticipating the clinical course of patients maintained on these