Edited* by Barry R. Bloom, Harvard School of Public Health, Boston, MA, and approved July 25, 2012 (received for review January 18, 2012)
Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.
Author contributions: C.J.G. and A.R.M. designed research; A.K.C., R.J.W., Y.H., V.N., P.T.E., K.I., P.M.T., T.R.V., G.H.B., G.E.P., M.D., R.N.D., H.J.M., L.V.B., R.D.B., C.A.M., L.B.-R., R.N., D.B.Y., F.A.D., C.J.G., and A.R.M. performed research; A.K.C. and A.R.M. analyzed data; and A.K.C. and A.R.M. wrote the paper.
Conflict of interest statement: Merck Serono donated €7,000 to Queen Mary University of London in 2010 to support an academic meeting entitled “Vitamin D: Mechanisms of Action in Health and Disease”; this meeting was convened by C.J.G. and A.R.M.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1200072109/-/DCSupplemental.
