Published ahead of print on April 26, 2007, doi:10.1164/rccm.200701-007OC
Am. J. Respir. Crit. Care Med., Volume 176, Number 2, July 2007, 208-213
A more recent version of this article appeared on July 15, 2007
Submitted on January 2, 2007
Accepted on April 26, 2007
A Single Dose of Vitamin D Enhances Immunity to Mycobacteria
Adrian R Martineau1*, Robert J Wilkinson2, Katalin A Wilkinson3, Sandra M Newton4, Beate Kampmann3, Bridget M Hall5, Geoffrey E Packe6, Robert N Davidson7, Sandra M Eldridge5, Zoe J Maunsell8, Sandra J Rainbow8, Jacqueline L Berry9, and Christopher J Griffiths5
1 Queen Mary's School of Medicine and Dentistry, Barts and The London, Centre for Health Sciences, London, United Kingdom; Newham Chest Clinic, Forest Gate, London, United Kingdom; Division of Medicine, Imperial College, Wright Fleming Institute, Wellcome Trust Centre for Research in Clinical Tropical Medicine, London, United Kingdom,
2 Division of Medicine, Imperial College, Wright Fleming Institute, Wellcome Trust Centre for Research in Clinical Tropical Medicine, London, United Kingdom; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, Cape Town, South Africa; Northwick Park Hospital, North West London Hospitals NHS Trust, Tuberculosis Clinic, London, United Kingdom,
3 Division of Medicine, Imperial College, Wright Fleming Institute, Wellcome Trust Centre for Research in Clinical Tropical Medicine, London, United Kingdom; Department of Medicine, Faculty of Health Sciences, University of Cape Town, Institute of Infectious Diseases and Molecular Medicine, Cape Town, South Africa,
4 Division of Medicine, Imperial College, Wright Fleming Institute, Wellcome Trust Centre for Research in Clinical Tropical Medicine, London, United Kingdom,
5 Queen Mary's School of Medicine and Dentistry, Barts and The London, Centre for Health Sciences, London, United Kingdom,
6 Newham Chest Clinic, Forest Gate, London, United Kingdom,
7 Northwick Park Hospital, North West London Hospitals NHS Trust, Tuberculosis Clinic, London, United Kingdom,
8 Department of Clinical Biochemistry, North West London Hospitals NHS Trust, London, United Kingdom,
9 Manchester Royal Infirmary, Vitamin D Research Group, University School of Medicine, Manchester, United Kingdom
* To whom correspondence should be addressed. E-mail: a.martineau{at}qmul.ac.uk.
Rationale: Vitamin D was used to treat tuberculosis in the pre-antibiotic 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 tuberculosis contacts in London, UK. 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) that measures the ability of whole blood to restrict luminescence, and thus growth, of recombinant reporter mycobacteria in vitro; the read-out is expressed as a luminescence ratio (luminescence post-infection/baseline luminescence). Interferon-gamma responses to the M. 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 to placebo (mean luminescence ratio at follow-up 0.57 vs. 0.71 respectively, 95% CI for difference 0.01 to 0.25; P=0.03) but did not affect antigen-stimulated Interferon-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 Interferon-gamma responses. Clinical trials should be performed to determine whether vitamin D supplementation prevents reactivation of latent tuberculosis infection.
Key words: Human, Vitamin D, Innate Immunity, Mycobacteria
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Copyright © 2007 American Thoracic Society
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