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
This article has been cited by other articles:
|
|
|
|
 
H. Friis, N. Range, M. L. Pedersen, C. Molgaard, J. Changalucha, H. Krarup, P. Magnussen, C. Soborg, and A. B. Andersen
Hypovitaminosis D Is Common among Pulmonary Tuberculosis Patients in Tanzania but Is Not Explained by the Acute Phase Response
J. Nutr.,
December 1, 2008;
138(12):
2474 - 2480.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. L. Wagner, F. R. Greer, and and the Section on Breastfeeding and Committee on
Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents
Pediatrics,
November 1, 2008;
122(5):
1142 - 1152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bouillon, G. Carmeliet, L. Verlinden, E. van Etten, A. Verstuyf, H. F. Luderer, L. Lieben, C. Mathieu, and M. Demay
Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice
Endocr. Rev.,
October 1, 2008;
29(6):
726 - 776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. H. White
Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity
Infect. Immun.,
September 1, 2008;
76(9):
3837 - 3843.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Heaney
Nutrients, Endpoints, and the Problem of Proof
J. Nutr.,
September 1, 2008;
138(9):
1591 - 1595.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. P. Heaney
Vitamin D in Health and Disease
Clin. J. Am. Soc. Nephrol.,
September 1, 2008;
3(5):
1535 - 1541.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Wagner, G. Sidhom, S. J. Whiting, D. Rousseau, and R. Vieth
The Bioavailability of Vitamin D from Fortified Cheeses and Supplements Is Equivalent in Adults
J. Nutr.,
July 1, 2008;
138(7):
1365 - 1371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Mansbach and C. A. Camargo Jr
Bronchiolitis: Lingering Questions About Its Definition and the Potential Role of Vitamin D
Pediatrics,
July 1, 2008;
122(1):
177 - 179.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. Martineau, R. J. Wilkinson, and C. J. Griffiths
Vitamin D and Tuberculosis Incidence in Spain
Am. J. Respir. Crit. Care Med.,
April 1, 2008;
177(7):
799 - 799.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Perez-Trallero, G. Cilla, A. Garcia-Zamalloa, and P. Idigoras
Vitamin D and Tuberculosis Incidence in Spain
Am. J. Respir. Crit. Care Med.,
April 1, 2008;
177(7):
798 - 798.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. C. McCann and B. N. Ames
Is there convincing biological or behavioral evidence linking vitamin D deficiency to brain dysfunction?
FASEB J,
April 1, 2008;
22(4):
982 - 1001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W. Yew and C. C. Leung
Update in Tuberculosis 2007
Am. J. Respir. Crit. Care Med.,
March 1, 2008;
177(5):
479 - 485.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. E Nnoaham and A. Clarke
Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis
Int. J. Epidemiol.,
February 1, 2008;
37(1):
113 - 119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zasloff
Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract
J. Am. Soc. Nephrol.,
November 1, 2007;
18(11):
2810 - 2816.
[Abstract]
[Full Text]
[PDF]
|
|
|
Copyright © 2007 American Thoracic Society
|
|
|
