1, 25 Dihydroxyvitamin D3 modulated cytokine response in pulmonary tuberculosis

1, 25 Dihydroxyvitamin D(3) (1, 25(OH)(2) D(3)) has gained significant importance in tuberculosis with regard to its immunoregulatory activities. Our aim was to evaluate the effect of 1, 25(OH)(2) D(3) on cytokine response to Mycobacterium tuberculosis antigens in pulmonary tuberculosis. Peripheral blood mononuclear cells obtained from 60 healthy controls and 52 pulmonary tuberculosis patients were cultured with culture filtrate antigen (CFA) of M. tuberculosis and live M. tuberculosis with and without 1, 25(OH)(2) D(3) (10(-9), 10(-8)and 10(-7)M concentrations). The culture supernatants were used to estimate IL-8, IL-6, TGF-beta, IL-10, IFN-gamma, IL-12p40, IL-2, IL-4 and IL-5 levels by ELISA. 1, 25 Dihydroxyvitamin D(3) significantly suppressed IL-12p40 and IFN-gamma production in response to CFA and live M. tuberculosis with a maximum suppression at 10(-7)M concentration (p<0.0001). In CFA stimulated cultures, addition of 1, 25(OH)(2) D(3) significantly suppressed IL-8, IL-6 and IL-10 whereas the IL-2 levels were significantly increased in controls. It variably influenced the Th2 cytokines, showing an increased trend for IL-4 and suppressed IL-5 levels. We report that 1, 25(OH)(2) D(3) differentially modulates production of cytokines in response to M. tuberculosis antigens by predominantly suppressing IL-12p40 and IFN-gamma production in a dose dependent manner. Our results suggest a role for vitamin D in restricting acquired immune response against tuberculosis by regulating cytokine production.