Donor pretreatment with leflunomide has an adverse effect on rat cardiac allograft survival

The effect of leflunomide (Lef) donor pretreatment (DPT) on rat cardiac allograft survival was investigated. In untreated Lewis recipients of untreated DA hearts, median graft survival was 5 days. DPT (Lef 5 or 10 mg/kg per day for 30 days) reduced median graft survival to 4.0 and 4.5 days, respectively. In immunosuppressed (Lef 5 mg/kg for 10 or 30 days) Lewis recipients of untreated DA hearts, median graft survival was 21 and 33 days, respectively. DPT with Lef 5 mg/kg per day for 5 days or 30 days reduced median graft survival to 12 and 23.5 days, respectively (p < 0.05). DPT with Lef resulted in earlier graft rejection but the histological appearance at the time of rejection was the same as in untreated controls. DPT with Lef resulted in a 40% reduction in MHC class II-positive cells in the heart. Histological examination of rejecting hearts showed no obvious difference in the nature of the rejection process between DPT and untreated control hearts. The paradox between class II reduction but earlier rejection indicates that DPT is exerting a deleterious effect through some unrecognized property of the graft.