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

1,25-Dihydroxyvitamin [D.sub.3] [1,25-[(OH).sub.2]-[D.sub.3]] is known to be an immunosuppressive hormone. This review primarily deals with in vitro and in vivo effects of 1,25-[(OH).sub.2]-[D.sub.3] and analogue, 1,25-dihydroxy-16ene-vitamin [D.sub.3] [l,25-[(OH).sub.2]-16ene-[D.sub.3]], on T helper subsets type 1 ([Th.sub.1]) or type 2 ([Th.sub.2]) that have distinctive functional characteristics in humans. [Th.sub.1] secrete interferon (IFN-[Gamma]), interleukin (IL-2) and induce B cells to produce immunoglobulin Ig[G.sub.2a] while [Th.sub.2] secrete IL-4, IL-10 and induce the production of Ig[G.sub.1] 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 [Th.sub.1]. In addition, 1,25-[(OH).sub.2]-[D.sub.3] directly inhibits IFN-[Gamma] secretion by [Th.sub.1] clones while it has little effect on IL-4 secretion by [Th.sub.2] clones. The analogue, 1,25-[(OH).sub.2]-16ene-[D.sub.3], is 100-fold more potent than 1,25-[(OH).sub.2]-[D.sub.3] 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 [Th.sub.1] induce Ig[G.sub.2a] responses. These actions of the vitamin [D.sub.3] compounds suggest that it may have potential therapeutic applications in [Th.sub.1]-mediated clinical situations such as autoimmunity and transplantation. INDEXING KEY WORDS: 1,25-dihydroxyvitamin [D.sub.3]; T helper cell subset Type 1; interleukin-12; encephalomyelitis; lupus