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Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment

Coussens, Anna K., Wilkinson, Robert J., Hanifa, Yasmeen, Nikolayevskyy, Vladyslav, Elkington, Paul T., Islam, Kamrul, Timms, Peter M., Venton, Timothy R., Bothamley, Graham H., Packe, Geoffrey E., Darmalingam, Mathina, Davidson, Robert N., Milburn, Heather J., Baker, Lucy V., Barker, Richard D., Mein, Charles A., Bhaw-Rosun, Leena, Nuamah, Rosamond, Young, Douglas B., Drobniewski, Francis A., Griffiths, Christopher J., Martineau, Adrian R.
Proceedings of the National Academy of Sciences of the United States of America 2012 v.109 no.38 pp. 15449-15454
25-hydroxycholecalciferol, anti-infective properties, chemokine CCL5, clinical trials, drug therapy, humans, immune response, immunomodulation, inflammation, interferon-alpha, interleukin-4, longitudinal studies, metabolites, mortality, patients, placebos, risk, secretion, tuberculosis
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.