Immunosuppressive actions of 1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions

Abstract

1,25-Dihydroxyvitamin D3 [1,25-(OH)2-D3] is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25-(OH)2-D3 and analogue, 1,25-dihydroxy-16ene-vitamin D3 [1,25-(OH)2-16ene-D3], on T helper subsets type 1 (Th1) or type 2 (Th2) that have distinctive functional characteristics in humans. Th1 secrete interferon (IFN-gamma), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG2a while Th2 secrete IL-4, IL-10 and induce the production of IgG1 and IgE by B cells. The sterol inhibits the secretion of IL-12, a cytokine produced by monocytes and B cells, which leads to the activation and differentiation of Th1. In addition, 1,25-(OH)2-D3 directly inhibits IFN-gamma secretion by Th1 clones while it has little effect on IL-4 secretion by Th2 clones. The analogue, 1,25-(OH)2-16ene-D3, is 100-fold more potent than 1,25-(OH)2-D3 in inhibiting IFN-gamma secretion but also has little effect on IL-4 secretion. In mice, when given in vivo, the sterol prevents the induction of spontaneous and induced autoimmune diseases and inhibits Th1 induce IgG2a responses. These actions of the vitamin D3 compounds suggest that it may have potential therapeutic applications in Th1-mediated clinical situations such as autoimmunity and transplantation.