Prolongation of allograft survival by 1,25-dihydroxyvitamin D₃

Background. 1,25-Dihydroxyvitamin D₃, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, both in vitro and in viva, preventing the development of several autoimmune diseases. These studies suggest that 1,25-dihydroxyvitamin D₃ may be effective in prolonging allograph survival. Methods. To test the hypothesis that 1,25- dihydroxyvitamin D₃ would prolong allograft survival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25- dihydroxyvitamin D₂ (200 ng/day) or 1,25-dihydroxyvitamin D₃ (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D₃ in prolonging graft survival in a vacularized model was determined by heterotopic ACI to Lewis heart transplants. Results. The provision of exogenous 1,25-dihydroxyvitamin D₃ or an analog, 19-nor-1,25- dihydroxyvitamin D₂, to mice markedly prolonged the survival of neonatal mouse heart allografts. Similar results were obtained with a vascularized heterotopic heart transplant model in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved less effective than 1,25-dihydroxyvitamin D₃. Graft survival in mice differing at class I and class II loci (B10.A(4R) → C57BL/10) increased from 13.0±1.1 days to 51.0±5.6 days and was significantly better than cyclosporine monotherapy (33.2±3.6). Rat heart survival in a high responder strain combination (ACI → Lewis) increased from 6.2±0.3 to 25.2±2.8 days. The increased survival of the transplants brought about with 1,25-dihydroxyvitamin D₃ was not accompanied by hypercalcemia in rats. Conclusion. These results suggest that 1,25-dihydroxyvitamin D₃ can be used as an effective agent in preventing graft rejection.