COMBINATION LEFLUNOMIDE AND CYCLOSPORINE PREVENTS REJECTION OF FUNCTIONAL WHOLE LIMB ALLOGRAFTS IN THE RAT

Whole rear limbs were transplanted from Brown Norway or Lewis rat dono rs to Lewis rat recipients (n=6 per group). One group of allograft rec ipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclo sporine (5 mg/kg/24 hr/orally) starting 2 days before to surgery. Trea tment continued for 60 days or until graft rejection. Untreated allogr afts were rejected over 6-8 days. After isograft transplantation, weig ht bearing began by day 17-25 after surgery. Sensory function was rest ored by 50 days after surgery, All allografts in the drug-treated grou p survived the 60-day period; survival in this group was significantly longer (P=0.0001) than the untreated controls. Weight bearing began b y day 30, but was incomplete in two rats at 60 days. Peroneal nerve fu nction was present in half the rats at 60 days after surgery. Leflunom ide combined with cyclosporine prevented whole limb allograft rejectio n across a major histocompatibility barrier.