Prolongation of allograft survival by 1,25-dihydroxyvitamin D3

Debra A. Hullett, Margherita Teresa-Anna Cantorna, Claudio Redaelli, Jean Humpal-Winter, Colleen E. Hayes, Hans W. Sollinger, Hector F. Deluca

Research output: Contribution to journalArticle

104 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)824-828
Number of pages5
JournalTransplantation
Volume66
Issue number7
DOIs
Publication statusPublished - Oct 15 1998

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Hullett, D. A., Cantorna, M. T-A., Redaelli, C., Humpal-Winter, J., Hayes, C. E., Sollinger, H. W., & Deluca, H. F. (1998). Prolongation of allograft survival by 1,25-dihydroxyvitamin D3. Transplantation, 66(7), 824-828. https://doi.org/10.1097/00007890-199810150-00002