MYCOPHENOLATE MOFETIL IMMUNOSUPPRESSION IN RAT PANCREAS ALLOTRANSPLANTATION

Prolongation of pancreas allograft survival has been difficult to achi eve in rodent models despite use of immunosuppression regimens that su ccessfully increase graft survival of other organs. The purpose of thi s study was to evaluate a new immunosuppressive agent, mycophenolate m ofetil (MM), for its ability to prevent rejection in a rat pancreas tr ansplant model. In addition, using congenic strains of rats, the effic acy of MM in rat pancreas transplantation was treated in the context o f isolated class I or class II major histocompatibility (MHC) differen ces. MM in doses of 12.5 to 37 mg/kg significantly prolonged BUF to LE W heart transplant survival beyond a 14-day course of therapy thereby demonstrating its immunosuppressive efficacy. In similar pancreas tran splant experiments, however, most grafts were rejected during the peri od of MM administration. Combination therapy with MM and cyclosporine did not extend pancreas survival beyond that achieved with RIM alone ( Mean Survival Time of 13.8 +/- 2.7 vs 11.7 +/- 1.6 days, respectively) . Conversely, combined therapy with MM and antilymphocyte serum achiev ed a mean survival for BUF to LEW pancreas transplants of 52.3 +/- 24. 8 days, which was significantly longer than that observed for either M M (11.7 +/- 1.6) or ALS (18.0 +/- 7.6) alone. MM therapy doubled pancr eas allograft survival when used in the face of class I MHC disparity and compared to controls (19.5 +/- 1.0 vs 10.0 +/- 1.9 days) but did n ot prolong grafts that were disparate at only the class II locus (12.6 +/- 1.5 vs 12.0 +/- 1.2 days, respectively, for MM vs control). These data indicate that MM may not be an effective single agent immunosupp ressive for pancreas transplantation except when MHC disparity is limi ted to the class I locus. (C) 1996 Academic Press, Inc.