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, 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. DrobniewskiChristopher J. Griffiths, Adrian R. Martineau*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    262 Citations (Scopus)

    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 antigenstimulated 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.

    Original languageEnglish
    Pages (from-to)15449-15454
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume109
    Issue number38
    DOIs
    Publication statusPublished - 18 Sept 2012

    Bibliographical note

    Copyright:
    Copyright 2013 Elsevier B.V., All rights reserved.

    Keywords

    • Adjunctive therapy
    • Antimicrobial peptides
    • Immunomodulation
    • Matrix metalloproteinases
    • Steroid hormones

    Fingerprint

    Dive into the research topics of 'Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment'. Together they form a unique fingerprint.

    Cite this