Total orthotopic allogeneic small bowel transplantation in rats: Effect of allograft irradiation combined with cyclosporine-A therapy

Rejection and graft versus host disease are prominent features in small bowel allotransplantation in rats. Cyclosporine treatment of the recipient and irradiation of the donor were used to circumvent these phenomena in the WAG to brown Norway rat model. Irradiation of the donor with five or 10 Gy did prevent graft versus host disease but resulted in a more vigorous rejection of small bowel allografts in untreated recipients (mean (SEM) survival times of 11.5 (0.4) (n = 8) and 7.5 (0.9) (n = 11) days respectively, versus 16.6 (2.6) days (n = 17), p < 0.01). Cyclosporine treatment of the recipient (25 mg/kg on days 0, 1, 2, 4, and 6 after transplantation) led to a mean (SEM) survival time of 38.3 (8.5) days (n = 10); 20% of the animals developed graft versus host disease. Combined with 5 Gy donor pretreatment, a similar survival was obtained without occurrence of graft versus host disease. However, cyclosporine treatment combined with 10 Gy led to a significant shortening of graft survival (23.1 (6.8) days, n = 9). These results suggest that although irradiation is very effective in preventing graft versus host disease, high dosages may accelerate rejection either by making the graft more vulnerable to rejection or by completely removing the immunosuppressive effect of graft versus host disease.