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单剂量维生素D可增强对分枝杆菌的免疫力。

A single dose of vitamin D enhances immunity to mycobacteria.

作者信息

Martineau Adrian R, Wilkinson Robert J, Wilkinson Katalin A, Newton Sandra M, Kampmann Beate, Hall Bridget M, Packe Geoffrey E, Davidson Robert N, Eldridge Sandra M, Maunsell Zoë J, Rainbow Sandra J, Berry Jacqueline L, Griffiths Christopher J

机构信息

Centre for Health Sciences, Queen Mary's School of Medicine and Dentistry, Barts and The London, and Department of Clinical Biochemistry, North West London Hospitals NHS Trust, Northwick Park Hospital, Harrow, E1 2AT, UK.

出版信息

Am J Respir Crit Care Med. 2007 Jul 15;176(2):208-13. doi: 10.1164/rccm.200701-007OC. Epub 2007 Apr 26.

DOI:10.1164/rccm.200701-007OC
PMID:17463418
Abstract

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).

摘要

理论依据

在抗生素时代之前,维生素D曾被用于治疗结核病(TB)。此前尚未进行过评估补充维生素D对抗分枝杆菌免疫作用的前瞻性研究。

目的

确定补充维生素D对抗分枝杆菌免疫和维生素D状态的影响。

方法

在英国伦敦对192名健康的成年结核接触者进行了一项双盲随机对照试验。参与者被随机分配接受单次口服2.5毫克维生素D或安慰剂,并在6周后进行随访。

测量指标与主要结果

主要结局指标采用功能性全血检测(卡介苗 - 荧光素酶检测)进行评估,该检测可测量全血在体外限制重组报告分枝杆菌发光从而限制其生长的能力;结果以发光比率(感染后发光/基线发光)表示。通过第二项全血检测确定对结核分枝杆菌抗原早期分泌性抗原靶标-6和培养滤液蛋白10的干扰素-γ反应。与安慰剂相比,补充维生素D显著增强了参与者全血在体外限制卡介苗-荧光素酶发光的能力(随访时的平均发光比率分别为0.57和0.71;差异的95%置信区间为0.01 - 0.25;p = 0.03),但不影响抗原刺激的干扰素-γ分泌。

结论

单次口服2.5毫克维生素D显著增强了参与者全血在体外限制卡介苗-荧光素酶发光的能力,且不影响抗原刺激的干扰素-γ反应。应进行临床试验以确定补充维生素D是否能预防潜伏性结核感染的再激活。在www.clinicaltrials.gov注册的临床试验(NCT 00157066)。

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