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 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 vascularized 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.


CONCLUSIONS
These results suggest that 1,25-dihydroxyvitamin D3 can be used as an effective agent in preventing graft rejection.
Hullett
D A
DA
Department of Biochemistry, University of Wisconsin-Madison, 53706, USA.
Cantorna
M T
MT
Redaelli
C
C
Humpal-Winter
J
J
Hayes
C E
CE
Sollinger
H W
HW
Deluca
H F
HF
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D006934:Hypercalcemia / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002117:Calcitriol