Successful treatment of acute, ongoing rat lung allograft rejection with the novel immunosuppressant SDZ-RAD

Background. Recent experimental data have shown that coadministration of mi croemulsion cyclosporine and the novel immunosuppressant SDZ-RAD potentiate s the immunosuppressive efficacies of both drugs to suppress allograft reje ction. Our study was designed to assess the potential of delayed SDZ-RAD ad ministration, in addition to cyclosporine maintenance therapy, to reverse a cute rejection in an allogeneic rat lung transplant model. Methods. Unilateral left lung transplantation was performed using Brown-Nor way donors implanted into Lewis recipients. An untreated control group and a cyclosporine monotherapy group (7.5 mg/kg) were followed for 7 days. An a dditional cyclosporine monotherapy group (7.5 mg/kg), and a combined therap y group treated with cyclosporine (7.5 mg/kg) plus SDZ-RAD (2.5 mg/kg), wer e followed for 21 days. For treatment of ongoing rejection, 7.5 mg/kg cyclo sporine was given as maintenance therapy, and SDZ-RAD (2.5 mg/kg) was added on postoperative day 7. Drugs were given orally, and in the combined thera py regimens, administered 6 hours apart. Outcome variables included daily w eight, radiographs, and histology. Results. Radiographs on postoperative day 7 showed mad and moderate opacifi cation of the left chest in the cyclosporine monotherapy groups and the unt reated control group. Addition of SDZ-RAD to cyclosporine treatment on post operative day 7 reversed opacification by postoperative days 14 and 21. Mon otherapy with micro-emulsion CsA resulted in mild histological rejection by day 7, which progressed to moderate rejection by day 21 Addition of SDZ-RA D on postoperative day 7 reversed acute rejection, resulting in none or min imal rejection at day 21. Conclusions. SDZ RAD reverses acute rejection under cyclosporine maintenanc e therapy in a stringent lung allotransplant model.