Effects of adding steroids, in vitro irradiation, or both to cyclosporine, immunosuppression in the murine laryngeal transplantation model

Adding oral prednisone or in vitro organ irradiation to an immunosuppressive regimen for laryngeal transplantation may allow cyclosporine dosage to be decreased without compromising organ rejection rates. Using an established rat laryngeal transplant model, we sought to determine whether combined immunosuppressive regimens decreased rejection rates. Twenty-two treatment groups of 10 animals each were studied. Cyclosporine was administered at 2 different historically low dosages (1.5 and 2 mg/kg per day) alone, in combination with prednisone, and with in vitro irradiation of the harvested larynx. At 15 days after transplantation, cyclosporine combined with prednisone did not significantly alter the mean severity of rejection. At 30 days after transplantation, rats treated with a combination of cyclosporine 2 mg/kg and prednisone 1 mg/kg showed the least amount of rejection. Rejection rates were significantly higher with 2 mg/kg cyclosporine alone (p<.00024). Irradiation did not significantly decrease the severity of rejection. These results demonstrate that at 1 month after transplantation, a combined steroid and cyclosporine regimen reduces the severity of rejection after laryngeal transplantation in an animal model. Our findings suggest that laryngeal transplant patients may be treated with low cyclosporine doses without experiencing organ rejection if steroids are added to the immunosuppressive regimen.