title: Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment.
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.
authors.affiliation: Division of Mycobacterial Research, Medical Research Council National Institute for Medical Research, London, United Kingdom.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Coussens
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wilkinson
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Hanifa
authors.forename: Vladyslav
authors.initials: V
authors.lastname: Nikolayevskyy
authors.forename: Paul T
authors.initials: PT
authors.lastname: Elkington
authors.forename: Kamrul
authors.initials: K
authors.lastname: Islam
authors.forename: Peter M
authors.initials: PM
authors.lastname: Timms
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Venton
authors.forename: Graham H
authors.initials: GH
authors.lastname: Bothamley
authors.forename: Geoffrey E
authors.initials: GE
authors.lastname: Packe
authors.forename: Mathina
authors.initials: M
authors.lastname: Darmalingam
authors.forename: Robert N
authors.initials: RN
authors.lastname: Davidson
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Milburn
authors.forename: Lucy V
authors.initials: LV
authors.lastname: Baker
authors.forename: Richard D
authors.initials: RD
authors.lastname: Barker
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Leena
authors.initials: L
authors.lastname: Bhaw-Rosun
authors.forename: Rosamond
authors.initials: R
authors.lastname: Nuamah
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Francis A
authors.initials: FA
authors.lastname: Drobniewski
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Griffiths
authors.forename: Adrian R
authors.initials: AR
authors.lastname: Martineau
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007107:Immune System; D007249:Inflammation; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012306:Risk; D013256:Steroids / Q000737:chemistry; D013997:Time Factors; D014376:Tuberculosis / Q000276:immunology* / Q000628:therapy; D014807:Vitamin D / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents; D013256:Steroids; D014807:Vitamin D