Molecular action of new immunosuppressive agents

Hippokratia 1998, 2(4):147-156

G Vergoulas


In kidney transplantation the ultimate target is “intelligent immunosuppression” where we look at each patient and ask whether he is going to be high or low responder to the transplant, whether he needs mono, double, triple or quadruple induction therapy. Our aim is to avoid rejection but at the same time to avoid life threatening infection and malignancy by over immunosuppression, to establish the correct drug dosage, to reduce or stop steroids whenever possible and to minimize side – effects. To do that we need to know about the immunogenetic make-up of the recipient and the mode of action of the drugs concerned.The last forty years there was plenty of time for somebody to get used with an immunosuppressive agent until the appearance of a new one. Now this is not valid. The last few years many new immunosuppressive agents have appeared and are in the final clinical testing or have been approved for clinical use. The development of these new drugs represents a trend for more specific immunosuppression. None of the new drugs has as target the fall of the number of white blood cells and their action targets the function mainly of ? lymphocytes which have been proved to play a central role in the specific immune response of the acute allograft rejection. The new immunosuppressive agents are drugs that either bind with cytoplasmic immunophilines (eg tacrolimus and sirolimus), block purine biosynthesis (mycophenolate mofetil) or finally are antibodies (chimeric and hummanized ) that bind with the IL-2 receptor.