Mécanismes moléculaires de l'activité des immunosuppresseurs actuels en transplantation : rôles du pharmacien

Immunosuppressive drugs modulate cellular and humoral immune response in the acute allograft rejection. The panel of drugs, which has been recently extended, allowed a significant progress for immunosuppressive treatment. These drugs help us to improve our knowledge of lymphocyte activation pathways. Corticoids, the oldest immunosuppresive drugs, inhibit many cytokines such as interleukin 2 (IL2) and interleukin 6. They represent the treatment of acute rejection. The other immunosuppressive drugs are used for preventing acute rejection. After binding to a specific immunophillin, cyclosporin and tacrolimus inhibit calcineurine, a serine/threonine phosphatase which plays a major role in cytokines transcription notably IL2 after T-cell activation. Anti-IL2 receptor monoclonal antibodies block IL2 activity following T-cell activation. Protein mammalian target of rapamycin inhibitors avoid the transcription of different mRNA involved in the regulation of the cellular cycle. These new agents are rapamycin or sirolimus and everolimus. The inhibitors of pyrimidic and puric bases synthesis, mycophenolic acid and azathioprin, inhibit T- and B-cell proliferation. The wide variety of immunosuppressive drugs permits the use of combinations, which aims at decreasing the immunologic risk and their own toxicities, notably nephrotoxicity. Before transplant, the pharmacist plays an important role in the prevention of initial pathologies and in the politic of organ donation. After transplant, the pharmacist has a role in the pharmacological and biological monitoring of immunosuppressive drugs. But the pharmacist must be involved in the optimization of therapeutics and in the education of transplant patients.