2-CHLORODEOXYADENOSINE (CLADRIBINE) IN COMBINATION WITH LOW-DOSE CYCLOSPORINE PREVENTS REJECTION AFTER ALLOGENEIC HEART AND LIVER-TRANSPLANTATION IN THE RAT

The purine analogue 2-chlorodeoxyadenosine (2-CDA) has been shown to p ossess synergistic immunosuppressive properties when given together wi th cyclosporin (CSA) in a rat small bowel transplant model. The presen t study investigated the immunosuppressive potency of 2-CDA alone and in combination after liver or heart transplantation in a fully allogen eic rat model with 5 animals in each group. Immunosuppression was prov ided with CSA 10 mg/kg body weight (BW)/day orally or 2-CDA 0.1 mg/kg/ BW day intravenously or both compounds together in the dosages mention ed. Animals were sacrificed on day 10 following transplantation, and g raft histology was assessed. In addition, cardiac graft function was e valuated by palpation immediately prior to sacrificing the animal. CSA given alone was able to mitigate but not prevent rejection. 2-CDA alo ne did not exhibit any detectable immunosuppressive effect. When CSA w as combined with 2-CDA, no rejection was seen in 80% of the liver allo grafts and in 60% of heart allografts, and only mild rejection was obs erved in the remaining animals. All hearts of the combined treatment g roup, however, beat strongly. From these findings it is concluded that 2-CDA alone has no, but together with CSA a strong immunosuppressive effect in preventing solid organ allograft rejection.