Inhibition of production and function of interleukin-6 by 1,25-dihydroxyvitamin D3.
1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to interfere with immunoglobulin production and lymphocyte proliferation in vitro. These lymphocyte functions are influenced by interleukin (IL)-6 produced by antigen presenting cells. Hence, the ability of 1,25-(OH)2D3 to interfere with the production and function of IL-6 was investigated. 1,25-(OH)2D3 and the analogue MC 903 inhibited IL-6 production by LPS-stimulated human mononuclear cells. The precursor 25-OH D3 was ineffective. Likewise, 1,25-(OH)2D3 but not 25-OH D3 inhibited rIL-6-driven as well as rIL-1 alpha/beta-driven proliferation of murine thymocytes. This effect of 1,25-(OH)2D3 was partially or totally overcome by larger concentrations of rIL-6 as well as by rIL-2 and ionomycin. Consistently, the production of IL-6 and IL-2 in rIL-1 driven thymocyte cultures were found to be reduced by 1,25-(OH)2D3. Inhibition of production and function of IL-6 may therefore be involved in 1,25-(OH)2D3-mediated regulation of lymphocyte functions in vitro.
Müller
K
K
Laboratory for Medical Immunology, Rigshospitalet (State University Hospital), Copenhagen, Denmark.
Diamant
M
M
Bendtzen
K
K
D000818:Animals; D002112:Calcifediol / Q000494:pharmacology; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D003864:Depression, Chemical; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
D002112:Calcifediol; D002117:Calcitriol; D007376:Interleukin-2; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors; C055085:calcipotriene