1,25-Dihydroxyvitamin D3 prolongs graft survival without compromising host resistance to infection or bone mineral density.
BACKGROUND
Recently, we have shown that 1,25-dihydroxyvitamin D3 prolongs graft survival in mice and rats when the donor and recipient differ at two or more major histocompatability loci. Among the most serious side effects encountered with the currently available transplantation antirejection drugs are an increased susceptibility to infection and decreased bone mineralization. Our results suggest that 1,25-dihydroxyvitamin D3 prolongs graft survival without these side effects of bone loss and susceptibility to infection.


METHODS
We compared the ability of 1,25-dihydroxyvitamin D3-treated, nontreated, or cyclosporine (CsA)-treated mice to resist infection with Candida albicans and herpes simplex virus-1. To determine bone density, femurs were collected from nontreated, 1,25-dihydroxyvitamin D3-treated (50 ng/mouse/day), or CsA-treated (25 mg/kg/day) mice, and bone ash was determined.


RESULTS
Here we show that 1,25-dihydroxyvitamin D3 treatment does not increase the susceptibility of the host to fungal or viral infection. Furthermore, CsA causes bone loss, whereas 1,25-dihydroxyvitamin D3 actually increases bone mass.


CONCLUSIONS
The use of 1,25-dihydroxyvitamin D3 and its analogs to increase transplant survival will avoid bone loss and opportunistic infection, two important disadvantages of the most widely used transplant antirejection drugs--CsA and the glucocorticoids.
Cantorna
M T
MT
Department of Biochemistry, University of Wisconsin-Madison, 53706, USA.
Hullett
D A
DA
Redaelli
C
C
Brandt
C R
CR
Humpal-Winter
J
J
Sollinger
H W
HW
Deluca
H F
HF
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002117:Calcitriol / Q000009:adverse effects / Q000627:therapeutic use*; D002177:Candidiasis / Q000276:immunology* / Q000401:mortality; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D007113:Immunity, Innate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007635:Keratitis, Dendritic / Q000276:immunology* / Q000401:mortality; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002117:Calcitriol