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Immunosuppressive Actions of 1,25-Dihydroxyvitamin D₃: Preferential Inhibition of Th₁ Functions^1,2,

Jacques M. Lemire^*,3, D. Clay Archer^*, Lucinda Beck and Hans L. Spiegelberg

^* Division of Pediatric Nephrology Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of California at San Diego, La Jolla, CA 92093

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-), interleukin (IL-2) and induce B cells to produce immunoglobulin IgG_2a 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- 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- 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 IgG_2a 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.

KEY WORDS: • 1,25-dihydroxyvitamin D₃ • T helper cell subset Type 1 • interleukin-12 • encephalomyelitis • lupus

¹ Presented as part of the symposium "Pleiotropic Actions of Vitamin D" given at the Experimental Biology '94 meeting, Anaheim, CA, on April 26, 1994. This symposium was sponsored by the American Institute of Nutrition. Guest editor for this symposium was Anthony W. Norman, University of California, Riverside, CA.

² The work done in the authors laboratories was supported in part by NIH grants R29-DK-39024 (J.M.L.) and AI 31595 (H.L.S.).

³ To whom correspondence should be addressed: Division of Pediatric Nephrology, 0609-G, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0609.

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