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Published ahead of print on April 26, 2007, doi:10.1164/rccm.200701-007OC
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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 208-213, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200701-007OC

Original Article

A Single Dose of Vitamin D Enhances Immunity to Mycobacteria

Adrian R. Martineau1,2,3,*, Robert J. Wilkinson3,4,5,*, Katalin A. Wilkinson3,4, Sandra M. Newton3, Beate Kampmann3,4, Bridget M. Hall1, Geoffrey E. Packe2, Robert N. Davidson5, Sandra M. Eldridge1, Zoë J. Maunsell6, Sandra J. Rainbow6, Jacqueline L. Berry7 and Christopher J. Griffiths1

1 Centre for Health Sciences, Queen Mary's School of Medicine and Dentistry, Barts and The London, London, United Kingdom; Newham Chest Clinic, London, United Kingdom; 3 Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Wright Fleming Institute, Imperial College London, London, United Kingdom; 4 Institute of Infectious Diseases and Molecular Medicine and Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; 5 Tuberculosis Clinic and 6 Department of Clinical Biochemistry, North West London Hospitals NHS Trust, Northwick Park Hospital, Harrow, United Kingdom; and 7 Vitamin D Research Group, University School of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom

Correspondence and requests for reprints should be addressed to Adrian R. Martineau, M.R.C.P., Centre for Health Sciences, Queen Mary's School of Medicine and Dentistry, Barts and The London, London E1 2AT, UK. E-mail: a.martineau{at}qmul.ac.uk

Rationale: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not previously been performed.

Objectives: To determine the effect of vitamin D supplementation on antimycobacterial immunity and vitamin D status.

Methods: A double-blind randomized controlled trial was conducted in 192 healthy adult TB contacts in London, United Kingdom. Participants were randomized to receive a single oral dose of 2.5 mg vitamin D or placebo and followed up at 6 weeks.

Measurements and Main Results: The primary outcome measure was assessed with a functional whole blood assay (BCG-lux assay), which measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the readout is expressed as a luminescence ratio (luminescence postinfection/baseline luminescence). IFN-{gamma} responses to the Mycobacterium tuberculosis antigens early secretory antigenic target-6 and culture filtrate protein 10 were determined with a second whole blood assay. Vitamin D supplementation significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro compared with placebo (mean luminescence ratio at follow-up, 0.57, vs. 0.71, respectively; 95% confidence interval for difference, 0.01–0.25; p = 0.03) but did not affect antigen-stimulated IFN-{gamma} secretion.

Conclusions: A single oral dose of 2.5 mg vitamin D significantly enhanced the ability of participants' whole blood to restrict BCG-lux luminescence in vitro without affecting antigen-stimulated IFN-{gamma} responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent TB infection. Clinical trial registered with www.clinicaltrials.gov (NCT 00157066).

Key Words: human • vitamin D • innate immunity • mycobacteria


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Vitamin D was used to treat tuberculosis in the preantibiotic era, and 25-hydroxyvitamin D supports induction of antimycobacterial immunity in vitro. Studies to evaluate the effect of vitamin D supplementation on antimycobacterial immunity have not been performed.

What This Study Adds to the Field
A single oral dose of vitamin D significantly enhanced tuberculosis contacts' antimycobacterial immunity in vitro.

 



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