C © 2005 The American Society of Transplantation and the American Society of Transplant Surgeons doi: 10.1111/j.1600-6143.2005.01152.x Concurrent Antiviral and Immunosuppressive Activities of Leflunomide In Vivo

We previously reported that the immunosuppressive malononitrileamides leflunomide and FK778 exert an-tiviral activity against cytomegalovirus (CMV). In the current investigation, we tested the hypothesis that leflunomide exerts concurrent antiviral activity and immune suppression in CMV-infected cardiac allo-graft recipients. Lewis rats were transplanted with Brown Norway hearts and then inoculated with rat CMV. Plaque assay demonstrated that leflunomide (30 mg/kg/day) reduced viral loads by 4–6 logs, and that the reduction in viral load was unaffected by ad-ministration of uridine. Leflunomide was as effective as cyclosporine A (CsA) or tacrolimus in preservation of allograft integrity through day 28. These studies di-rectly demonstrate the bifunctionality of leflunomide as concurrently immunosuppressive and antiviral, en-hancing the promise of this agent as a clinical option for treatment of transplant recipients