TY - JOUR
T1 - Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment
AU - Coussens, Anna K.
AU - Wilkinson, Robert J.
AU - Hanifa, Yasmeen
AU - Nikolayevskyy, Vladyslav
AU - Elkington, Paul T.
AU - Islam, Kamrul
AU - Timms, Peter M.
AU - Venton, Timothy R.
AU - Bothamley, Graham H.
AU - Packe, Geoffrey E.
AU - Darmalingam, Mathina
AU - Davidson, Robert N.
AU - Milburn, Heather J.
AU - Baker, Lucy V.
AU - Barker, Richard D.
AU - Mein, Charles A.
AU - Bhaw-Rosun, Leena
AU - Nuamah, Rosamond
AU - Young, Douglas B.
AU - Drobniewski, Francis A.
AU - Griffiths, Christopher J.
AU - Martineau, Adrian R.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/9/18
Y1 - 2012/9/18
N2 - 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.
AB - 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.
KW - Adjunctive therapy
KW - Antimicrobial peptides
KW - Immunomodulation
KW - Matrix metalloproteinases
KW - Steroid hormones
UR - http://www.scopus.com/inward/record.url?scp=84866527671&partnerID=8YFLogxK
U2 - 10.1073/pnas.1200072109
DO - 10.1073/pnas.1200072109
M3 - Article
C2 - 22949664
AN - SCOPUS:84866527671
SN - 0027-8424
VL - 109
SP - 15449
EP - 15454
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 38
ER -