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A well-known association between vitamin D₃ and infection with Mycobacterium tuberculosis has previously been reported, but little is known regarding the underlying mechanisms. We have investigated how 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] affects the proinflammatory cytokine production induced by M. tuberculosis. Furthermore, we explored whether 1,25(OH)₂D₃ influence the production of the protective antimycobacterial peptide cathelicidin. Upon in vitro stimulation with M. tuberculosis, 1,25(OH)₂D₃ induced a dose-dependent down-regulation of IL-6, TNFα and IFNγ, while increasing the production of IL-10 in culture supernatant as well as cathelicidin mRNA expression. This effect on cytokine response was not due to modulation of T-helper cell differentiation, as T-bet, GATA3, Foxp3 and ROR-γt mRNA expression remained unaffected. Similarly, 1,25(OH)₂D₃ did not affect suppressor of cytokine …