Synergistic effect of triptolide and tacrolimus on rat cardiac allotransplantation.

Abstract

Recent studies have shown that triptolide inhibits T cell activation through mechanisms different from those of cyclosporine A and tacrolimus and we postulated that triptolide might have a synergistic effect with tacrolimus to enhance immunosuppression. Using a F344 donor-to-Lewis recipient rat combination, we investigated the immunosuppressive effects of triptolide alone or in combination with tacrolimus on the survival of cardiac allografts. Recipients were treated with placebo, triptolide, tacrolimus, and triptolide in combination with tacrolimus at different doses. The median survival time (MST) was 8 days for placebo; 9.5, 11, 14 and 19 days for triptolide monotherapy at doses of 0.04, 0.08, 0.16, and 0.32 mg/kg/day, respectively, and 11, 13.5, and 52 days for tacrolimus monotherapy at doses of 0.025, 0.05, and 0.1 mg/kg/day, respectively. Tacrolimus 0.025 mg/kg/day combined with triptolide 0.08 and 0.16 mg/kg/day prolonged the MST to 17.5 and 20 days, respectively; while tacrolimus 0.05 mg/kg/day combined with triptolide 0.04, 0.08, and 0.16 mg/kg/day prolonged the MST to 21, 23, and 23 days, respectively. These results suggest that triptolide is a moderately effective immunosuppressive agent. Triptolide combined with a subtherapeutic dose of tacrolimus produced a synergistic effect in prolonging rat cardiac allograft survival.