Results of vascularized joint allograft under immunosuppression with cyclosporine

The effects of cyclosporine (CsA), a strong immunosuppressive drug, on vascularized allogeneic joint transplantations were examined. An orthotopical transplant model of a vascularized knee joint allograft was developed using inbred DA and Lewis rats to investigate the fate of grafts following withdrawal of short-term immunosuppression compared to continuous immunosuppression with CsA. Five isograft controls acquired solid bone union at both femur and tibia sites within 4 weeks, and joint function as skeletal support was maintained until 25 weeks. Without immunosuppression, ten allografts were severely rejected within the first week, and joint destruction occurred immediately. Twenty-five short-term immunosuppressed rats acquired solid union, but, after withdrawal of immunosuppression, grafted joints showed gradual rejection and were destroyed due to pathological fractures or joint instability, although partial revascularization from the recipient occurred. Ten allografts under continuous immunosuppression at a dose of 10 mg/kg/day showed no rejection and remained viable for 12 weeks postoperatively, but thereafter all rats died. Death was considered to be a side effect of CsA. Fifteen animals, under continuous immunosuppression at a dose of 5 mg/kg/day, showed no rejection except in the bone marrow; the grafted joint function was not effected until 25 weeks. Continuous treatment with low and nontoxic doses (5 mg/kg/day) of CsA was necessary to maintain the functions of the grafted joint.