IMMUNOSUPPRESSIVE ACTIONS OF 1,25-DIHYDROXYVITAMIN D-3 - PREFERENTIALINHIBITION OF TH-1 FUNCTIONS

1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)-D-3] is known to be an immunos uppressive hormone. This review primarily deals with in vitro and in v ivo effects of 1,25-(OH)(2)-D-3 and analogue, 1,25-dihydroxy-16ene-vit amin D-3 [1,25-(OH)(2)-16ene-D-3], on T helper subsets type 1 (Th-1) o r type 2 (Th-2) that have distinctive functional characteristics in hu mans. Th, secrete interferon (IFN-gamma), interleukin (IL-2) and induc e B cells to produce immunoglobulin IgG(2a) while Th-2 secrete IL-4, I L-10 end induce the production of IgG(1) and IgE by B cells. The stero l inhibits the secretion of IL-12, a cytokine produced by monocytes an d B cells, which leads to the activation and differentiation of Th,. I n addition, 1,25-(OH)(2)-D-3 directly inhibits IFN-gamma secretion by Th, clones while it has little effect on IL-4 secretion by Th-2 clones . The analogue, 1,25-(OH)(2)-16ene-D-3, is 100-fold more potent than 1 ,25-(OH)(2)-D-3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prev ents the induction of spontaneous and induced autoimmune diseases and inhibits Th, induce IgG(2a) responses. These actions of the vitamin D- 3 compounds suggest that it may have potential therapeutic application s in Th-1-mediated clinical situations such as autoimmunity and transp lantation.