1, 25-DIHYDROXYVITAMIN D₃ (1, 25(OH)₂D₃) SUPPRESSES THE IN VITRO PROLIFERATION AND IM1UNOQABULIN PRODUCTION BY NORMAL HUMAN PERIPHERAL BLOOD CELLS

Abstract

A specific, high-affinity intracellular receptor for 1,25(OH)₂D₃ has recently been identified in peripheral mono-cytes and activated T and B lymphocytes from normal human subjects. However, a functional role for the 1,25(OH)₂D₃ receptor in these cells has yet to be identified, and led us to evaluate the effects of 1,25(OH)₂D₃ on lymphocyte activation. Peripheral blood mononuclear cells were isolated from four normal adult volunteers suspended in medium RMPI-1640 containing 10% FBS and activated with pokeweed mitogen or Candida albicans in the presence or absence of 10⁻⁷ to 10⁻¹⁰M 1,25(OH)₂D₃ . DNA synthesis was assessed by [³H]-thymidine incorporation on day 5 of culture, and immunoglobulin production was determined by enzyme-linked immunoabsorbent assay (ELISA) on day 12. 1,25(OH)₂D₃ inhibited DNA and immunoglobulin synthesis in cells from all four subjects in a dose-dependent fashion with maximal inhibition seen at 10⁻⁸M 1,25(OH)₂D₃. The specificity of the effect for 1,25 was confirmed by incubation of additional cultures with 25-OH-D₃ and 24,25(OH)₂D₃ (10⁻⁷ to 10⁻¹⁰M). Only 10⁻⁷M 24,25(OH)₂D₃ had a significant effect on immunoglobulin production. These data suggest a potential role for 1,25(OH)₂D₃ in modulation of the human immune response.

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