New immunosuppressive drugs: mechanistic insights and potential therapeutic advances

Together with CsA, the new macrolide immunosuppressants FK506 and rapamycin have proved to be valuable tools in providing new information about key molecular events that underlie lymphocyte activation and degranulation. Studies of their mechanisms of action have pinpointed the phosphatase calcineurin and protein kinases as important signaling mediators in T-cell activation. Other new immunosuppressive drugs, including leflunomide, mycophenolate mofetil, brequinar sodium and deoxyspergualin exhibit diverse inhibitory effects on cells of the immune system and offer considerable promise as adjunctive therapeutic immunosuppressants. FK506 appears to be both a valuable therapeutic alternative to liver or kidney retransplantation and an alternative primary immunosuppressant to CsA in hepatic (especially) and renal transplantation. There is now good evidence that immunosuppressive drugs, both old and new, permit the establishment of donor-derived, multi-lineage cell chimerism following organ transplantation.