1,25-DIHYDROXYVITAMIN D-3 PROLONGS GRAFT-SURVIVAL WITHOUT COMPROMISING HOST-RESISTANCE TO INFECTION OR BONE-MINERAL DENSITY

Background. Recently, we have shown that 1,25-dihydroxyvitamin D-3 pro longs graft survival in mice and rats when the donor and recipient dif fer at two or more major histocompatability loci. Among the most serio us side effects encountered with the currently available transplantati on antirejection drugs are an increased susceptibility to infection an d decreased bone mineralization, Our results suggest that 1,25-dihydro xyvitamin D3, prolongs graft survival without these side effects of bo ne loss and susceptibility to infection. Methods. We compared the abil ity of 1,25-dihydroxyvitamin D-3-treated, nontreated, or cyclosporine (CsA)-treated mice to resist infection with Candida albicans and herpe s simplex virus-1. To determine bone density, femurs were collected fr om nontreated, 1,25-dihydroxyvitamin D-3-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 D-3 treatment does not incre ase the susceptibility of the host to fungal or viral infection. Furth ermore, CsA causes bone loss, whereas 1,25-dihydroxyvitamin D-3 actual ly increases bone mass. Conclusions. The use of 1,25-dihydroxyvitamin D-3 and its analogs to increase transplant survival will avoid bone lo ss and opportunistic infection, two important disadvantages of the mos t widely used transplant antirejection drugs-CsA and the glucocorticoi ds.