This study compares the efficacy of long-term intermittent immunosuppression using cyclosporine-A, FK-506 (tacrolimus), and RS-61443 (mycophenolate mofetil) in preventing rejection of donor limb tissues in a standardized limb transplant model. The animals were divided into four experimental groups and all animals received immunosuppression until rejection was noted. Biopsies were obtained after euthanasia at the first signs of rejection. All animals in Group I (controls) showed signs of rejection with a mean time of 6.8 days. Mean rejection times in the experimental groups were: Group II (Cyclosporine-A) = 62 days; Group III (RS-61443) = 44 days; Group IV (FK-506) = 296 days. All of the animals in Group IV died of complications related to immunosuppression without showing signs of rejection at 273-334 days. Three of the 10 animals in Group III died without signs of rejection. Group IV also showed a significant difference when compared individually with Group III and Group II.
Limb transplantation in humans has been feasible for at least two decades. The persistent barrier to success has been the immunogenicity of the donor tissue and the inherent difficulties and dangers in preventing rejection. This study attempts to clarify the efficacy of three of the most commonly used immunosuppressive agents in transplant surgery: Cyclosporine-A, RS-61443, and FK-506. In this model, FK-506 is the most effective of the three drugs at preventing rejection of donor limbs across a major histocompatibility barrier. These results in the most immunologically incompatible rat strains is a very encouraging.