PARTIAL PREVENTION OF ACTIVE HEYMANN NEPHRITIS BY 1-ALPHA,25 DIHYDROXYVITAMIN D-3

The hormone 1 alpha, 25 dihydroxyvitamin D-3 (1,25(OH)(2)D-3) has pote nt immunosuppressive effects in vitro. Recent publications also descri bed a protective effect of the hormone in various animal models of imm une-mediated diseases. To test its in vivo activity we induced active Heymann nephritis in Lewis rats that were either untreated or treated with 1,25(OH)(2)D-3 or its synthetic 20-epi analogue, KH1060. Treatmen t with cyclosporine A (CsA) was used as an immunosuppressive control. In this nephrotic model the administration of 1,25(OH)(2)D-3 (0.5 mu g /kg body weight) given on alternate days during the first 13 days afte r active immunization significantly reduced the proteinuria as measure d by weeks 7-9. This reduction was comparable to the reduction observe d in rats treated with CsA (20 mg/kg) on alternate days. A second seri es of experiments with 1,25(OH)(2)D-3 confirmed these findings. The le vel of autoantibodies was found to be significantly suppressed during the treatment time in the CsA (20 mg/kg) group, whereas the limit of s ignificance (P=0.06) was reached in the 1,25(OH)(2)D-3 (0.5 mu g/kg) g roup. The size of the immune deposits also was found to be substantial ly smaller in the groups that developed less proteinuria. The administ ration of 1,25(OH)(2)D-3 transiently increased the mean serum calcium concentration with 2.5 mg/dl above the pretreatment values, and the ur inary calcium excretion by a factor of 3-5 during the short treatment time. Treatment with the analogue KH1060 did not reduce the proteinuri a significantly. Our experiments add evidence to the hypothesis that 1 ,25(OH)(2)D-3 in pharmacological doses has immunosuppressive potency.