Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.


Coussens, AK; Wilkinson, RJ; Hanifa, Y; Nikolayevskyy, V; Elkington, PT; Islam, K; Timms, PM; Venton, TR; Bothamley, GH; Packe, GE; Darmalingam, M; Davidson, RN; Milburn, HJ; Baker, LV; Barker, RD; Mein, CA; Bhaw-Rosun, L; Nuamah, R; Young, DB; Drobniewski, FA; Griffiths, CJ; Martineau, AR; (2012) Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment. Proceedings of the National Academy of Sciences of the United States of America, 109 (38). pp. 15449-54. ISSN 0027-8424 DOI: https://doi.org/10.1073/pnas.1200072109

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Abstract

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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 22949664
Web of Science ID: 309211000076
URI: http://researchonline.lshtm.ac.uk/id/eprint/768457

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