NEW IMMUNOSUPPRESSIVE DRUGS AND THEIR ROLE IN THE PREVENTION OF ISLETXENOGRAFT REJECTION

Islet transplantation offers an attractive future means to treat diabe tes as long as prevention of xenograft rejection can be accomplished. This review analyses the role of 5 new immunosuppressive drugs [tacrol imus, sirolimus, mycophenolate mofetil, gusperimus (15-deoxyspergualin ) and leflunomide] in the context of islet xenotransplantation. Althou gh cytotoxic T cells are the major effector cells in allogeneic islet rejection, macrophages serve as important contributing effector cells in xenogeneic islet rejection. All the drugs discussed in this review inhibit T cell activation, and several of them also inhibit B cells. I n addition, gusperimus has been found to inhibit macrophages. All the drugs have, at least in some animal model, delayed islet xenograft rej ection. Synergistic, or at least additive, protective effects have bee n observed when 2 or more of the drugs have been used in combination. Assessment of the relative efficacy of the various drugs is made diffi cult by the use of different models in the various studies performed. In the future, several drugs should be examined in a single model. The efficacy of the various drugs in controlling autoimmune beta cell dam age after transplantation remains poorly known. One of the drugs, tacr olimus, has the disadvantage of being diabetogenic in animals and huma ns. The other drugs do not disturb glucose homeostasis, at least in hu mans. Mycophenolate mofetil and leflunomide are antiproliferative drug s, a feature that might be disadvantageous in fetal endocrine pancreas transplantation. Although several of the newly available drugs show c onsiderable promise in the prevention of islet xenograft rejection, th e search for even better immunosuppressive drugs must continue.