Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.

Anna K Coussens; Robert J Wilkinson; Yasmeen Hanifa; Vladyslav Nikolayevskyy; Paul T Elkington; Kamrul Islam; Peter M Timms; Timothy R Venton; Graham H Bothamley; Geoffrey E Packe; +12 more... Mathina Darmalingam; Robert N Davidson; Heather J Milburn; Lucy V Baker; Richard D Barker; Charles A Mein; Leena Bhaw-Rosun; Rosamond Nuamah; Douglas B Young; Francis A Drobniewski; Christopher J Griffiths; Adrian R Martineau; (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. 15449-15454. ISSN 0027-8424 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-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.

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