A single dose of vitamin D enhances immunity to mycobacteria
A single dose of vitamin D enhances immunity to mycobacteria
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DOI：
10.1164/rccm.200701-007oc
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发表时间：
2007-07-15
影响因子：
24.7
通讯作者：
Griffiths, Christopher J.
中科院分区：
文献类型：
--
作者：
Martineau, Adrian R.;Wilkinson, Robert J.;Griffiths, Christopher J.
理论基础：在抗生素之前的时代，维生素D被用于治疗结核病。目的：探讨补充维生素D对抗分枝杆菌免疫功能和维生素D状态的影响。方法：对英国伦敦192名健康成人结核病接触者进行随机双盲对照试验。参与者被随机接受单次口服2.5毫克维生素D或安慰剂，并在6周内进行跟踪。测量和主要结果：主要结果测量采用功能全血试验(BCG-lux试验)进行评估，该方法测量全血在体外限制重组报告分枝杆菌发光从而生长的能力；读数表示为发光比率(感染后发光/基线发光)。用第二次全血试验检测结核分枝杆菌抗原、早期分泌型抗原Target-6和培养滤液蛋白10对干扰素-γ的反应。与安慰剂相比，补充维生素D显著提高了受试者全血在体外限制卡介苗发光的能力(平均发光比分别为0.57和0.71；95%可信区间为0.01-0.25；p=0.03)，但不影响抗原刺激的干扰素-γ的分泌。结论：单次口服2.5 mg维生素D可显著提高受试者全血在体外限制卡介苗发光的能力，而不影响抗原刺激的干扰素-γ反应。应该进行临床试验，以确定补充维生素D是否可以防止潜伏的结核病感染重新激活。临床试验在www.Clinicaltrials.gov网站注册(NCT 00157066)。
Rationale: Vitamin D was used to treat tuberculosis (TB) in the preantibiotic era. Prospective studies to evaluate the effect of vitamin D supplementation on anti mycobacterial 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 followup, 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).