Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production.
Human peripheral blood monocytes and activated, but not resting, lymphocytes possess specific intracellular receptors for the active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). The effects of 1,25-(OH)2D3 on the function of these cells was therefore examined. The addition of physiologic concentrations of the hormone (0.001-0.1 nM) to lectin- or antigen-activated lymphocytes resulted in inhibition of lymphocyte proliferation. Supernatants from lectin-activated lymphocytes incubated with 1,25-(OH)2D3 had reduced interleukin-2 (IL-2) activity. The immediate biological precursor of 1,25-(OH)2D3, 25-hydroxyvitamin D3, did not affect function of lymphocytes or monocytes. The ability of exogenous recombinant IL-2 to reverse the inhibitory effects of the hormone on lymphocyte proliferation suggest that 1,25-(OH)2D3 does not alter the generation of IL-2 receptors. In contrast to its effects on IL-2 production, 1,25-(OH)2D3 caused a dose-dependent increase in the production of interleukin-1 (IL-1) by monocyte/macrophages. These results suggest that immune cells and their products can be regulated in a specific but diverse fashion by the vitamin D3-endocrine system.
D000941:Antigens / Q000276:immunology; D001862:Bone Resorption / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D037102:Lectins / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects*; D015846:Monokines; D014176:Protein Biosynthesis
D000941:Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D037102:Lectins; D015846:Monokines; D002117:Calcitriol