[Selective immunosuppression with monoclonal antibodies against ICAM-1 and LFA-1 with FK 506 after experimental small intestine transplantation in the rat].
Prevention of allograft rejection remains a major problem after small bowel transplantation (SBT) and requires potent immunosuppressive regimens. In a variety of transplant models, e.g. liver or heart transplantation, the supplementary application of monoclonal antibodies (mabs) against adhesion molecules is effective in both prolonging graft survival and inducing long-term graft acceptance or tolerance in some cases. In this study anti ICAM-1 (1A29) and anti LFA-1 (WT1) mabs were used in combination with a subtherapeutic dose of FK 506 for 13 days after allogeneic SBT in the rat. The results of this study indicate that in contrast to the induction of allospecific tolerance after liver transplantation, the addition of anti ICAM-1 and/or of anti LFA-1 mabs after SBT reverses the FK 506 effect and results in early graft rejection. It has been shown that higher dosages of these mabs, given alone or in combination with CsA or FK 506, result in long-term survival of cardiac allografts in both, rats and mice [4-8]. Graft survival after pancreas transplantation is prolonged [6]. However, these negative therapeutic effects of the mabs 1A29 and WT1 after SBT have to be critically reevaluated and further analysed.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016042:Transplantation, Heterotopic
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D016559:Tacrolimus