Immunosuppression in cardiac transplantation: a new era in immunopharmacology

During the past 5 years, there has been a concerted effort to identify new immunosuppressive agents for organ transplantation that have greater efficacy and fewer side effects than current therapies (corticosteroids, azathioprine, cyclosporine, anti-T cell antibodies). These new drugs can be generally classified according to their varying structures or mechanisms of action: xenobiotic molecules (FK506, rapamycin, cyclosporine analogues); antimetabolites (mycophenolate mofetil, mizoribine, brequinar sodium); and those agents with novel or incompletely defined mechanisms of action (leflunomide, 15-deoxyspergualin). Many of the newer agents offer better therapeutic indexes, and some even show promise in the treatment of two of the major obstacles currently facing cardiac allograft transplantation: antibody-mediated accelerated humoral rejection and chronic vascular rejection (also known as accelerated graft coronary artery disease). With the increasing shortage of donor organs in recent years, there has been a resurgence of interest in xenotransplantation; some of the new immunosuppressants demonstrate efficacy in prolonging xenograft survival. Most of these agents will probably find their niches as components of low-dose combination regimens designed to maximize effective immunosuppression and minimize drug toxicities and opportunistic infections.