The central issue in organ transplantation remains suppressionof allograft rejection. Thus, development of immunosuppressivedrugs is the key to successful allograft function. Immunosuppressiveagents are used for induction (intense immunosuppression inthe initial days after transplantation), maintenance, and reversalof established rejection. This review focuses on agents thatare either approved or in phase 2 or phase 3 trials in kidneytransplantation, but many issues covered here are applicableto all organ transplantation. I begin with a model of the alloimmuneresponse to illustrate how these medications act.
Three-Signal Model of Alloimmune Responses
Alloimmune responses involve both naive and memory lymphocytes,1including lymphocytes previously . . . [Full Text of this Article]
Effectors and Lesions of Rejection
HostGraft Adaptation
Immunosuppressive Drugs
Classification of Immunosuppressive Drugs
Small-Molecule Drugs
Calcineurin Inhibitors
Inosine Monophosphate Dehydrogenase Inhibitors
Target-of-Rapamycin Inhibitors
Dihydroorotate Dehydrogenase Inhibitors
FTY720
Depleting Antibodies
Nondepleting Antibodies and Fusion Proteins
Daclizumab and Basiliximab
LEA29Y
Additional Drugs
Protocol Development and Emerging Issues
Source Information
From the Division of Nephrology and Transplantation Immunology, University of Alberta, Edmonton, Canada.
Address reprint requests to Dr. Halloran at 250 Heritage Medical Research Centre, Edmonton, AB T6G 2S2, Canada, or at phil.halloran@ualberta.ca.
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