Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Coussens, A.K., Wilkinson , R.J., Hanifa, Y., Nikolayevskyy, V., Elkington , P.T., Islam, K., Timms, P., Venton, T.R., Bothamley, G.H., Packe, G.E., Darmalingam, M., Davidson, R.N., Milburn, H.J., Baker, L.V., Barker, R.D., Mein, C.A., Bhaw-Rosun, L., Nuamah, R., Young, D.B., Drobniewski, F.A., Griffiths, C.J. and Martineau, A.R. (2012) Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. PNAS: Proceedings of the National Academy of Sciences of the United States of America, 109, 15449-54. (doi:10.1073/pnas.1200072109).


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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-?. 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.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1073/pnas.1200072109
ISSNs: 0027-8424 (print)
Related URLs:
Subjects: R Medicine > RC Internal medicine
Divisions : Faculty of Medicine > Clinical and Experimental Sciences
ePrint ID: 342551
Accepted Date and Publication Date:
4 September 2012Published
Date Deposited: 06 Sep 2012 13:25
Last Modified: 31 Mar 2016 14:33

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