PROLONGATION OF ALLOGRAFT SURVIVAL BY 1,25-DIHYDROXYVITAMIN D31

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Abstract

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 vivo, 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.

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