1α,25-Dihydroxyvitamin D3 inhibits γ-interferon synthesis by normal human peripheral blood lymphocytes

1α,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the biologically active metabolite of vitamin D3, inhibited synthesis of γ-interferon (IFN-γ) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-γ protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)2D3 concentration, 1,25-(OH)2D3 also inhibited accumulation of IFN-γ mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)2D3 to modulate IFN-γ protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-γ synthesis by PBLs was specific for 1,25-(OH)2D3; the potencies of other vitamin D3 metabolites were correlated with their affinities for the cellular 1,25-(OH)2D3 receptor. The time course of 1,25-(OH)2D3 receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)2D3-mediated inhibition of IFN-γ synthesis. Finally, the authors examined the effects of 1,25-(OH)2D3 on the constitutive IFN-γ production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-γ synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)2D3, whereas IFN-γ synthesis by Ab-VDR cells was not altered by 1,25-(OH)2D3. The data presented in this study provide evidence for a role of 1,25-(OH)2D3 in immunoregulation