PROLONGATION OF ALLOGRAFT SURVIVAL BY 1,25-DIHYDROXYVITAMIN D-3

Background. 1,25-Dihydroxyvitamin D-3, the hormonal form of vitamin D, is now believed to play a significant role in the immune responses, b oth in vitro and in vivo, preventing the development of several autoim mune diseases. These studies suggest that 1,25-dihydroxyvitamin D-3 ma y be effective in prolonging allograph survival. Methods. To test the hypothesis that 1,25-dihydroxyvitamin D-3 would prolong allograft surv ival, neonatal heart grafts were transplanted to allogeneic recipients receiving either 19-nor-1,25-dihydroxyvitamin D-2 (200 ng/day) or 1,2 5-dihydroxyvitamin D-3 (50 ng/mouse/day) orally through the diet. The efficacy of 1,25-dihydroxyvitamin D-3 in prolonging graft survival in a vacularized model was determined by heterotopic ACI to Lewis heart t ransplants. Results. The provision of exogenous 1,25-dihydroxyvitamin D-3 or an analog, 19-nor-1,25-dihydroxyvitamin D-2, to mice markedly p rolonged the survival of neonatal mouse heart allografts. Similar resu lts were obtained with a vascularized heterotopic heart transplant mod el in rats. Cyclosporine at a maximum 25 mg/kg dose for mice proved le ss effective than 1,25-dihydroxyvitamin D-3. Graft survival in mice di ffering at class I and class II loci (B10.A(4R) --> C57BL/10) increase d 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 h igh responder strain combination (ACI --> Lewis) increased from 6.2+/- 0.3 to 25.2+/-2.8 days. The increased survival of the transplants brou ght about with 1,25-dihydroxyvitamin D-3 was not accompanied by hyperc alcemia in rats. Conclusion. These results suggest that 1,25-dihydroxy vitamin D-3 can be used as an effective agent in preventing graft reje ction.