Abstract

 
 
 
 Background: Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. In the lung, alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. The objective of this study was to determine the effects of vitamin D supplementation on gene expression of alveolar macrophages.
 Methods: We performed a parallel, double-blind, placebo-controlled, randomized trial to determine the effects of vitamin D on alveolar macrophage gene expression. Vitamin D3 (1000 international units/day) or placebo was administered to adults for three months. Bronchoscopy was performed pre- and post-intervention to obtain alveolar macrophages. Messenger RNA was isolated from the macrophages and subjected to whole genome exon array analysis. The primary outcome was differential gene expression of the alveolar macrophage in response to vitamin D supplementation. Specific genes underwent validation by polymerase chain reaction methods.
 Results: Fifty-eight subjects were randomized to vitamin D (n = 28) or placebo (n = 30). There was a marginal overall difference between treatment group and placebo group in the change of 25-hydroxyvitaminD levels(4.43 ng/ml vs. 0.2 ng/ml, p = 0.10). Whole genome exon array analysis revealed differential gene expression associated with change in serum vitamin D levels in the treated group. CCL8/MCP-2 was the top-regulated cytokine gene and was further validated.
 Conclusions: Although only a non-significant increased trend was seen in serum vitamin D levels, subjects treated with vitamin D supplementation had immune-related differential gene expression in alveolar macrophages.
 Trial registration: ClinicalTrials.org: NCT01967628.
 
 
 
Highlights
Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases
Trial design This study was performed as a specific analysis of a double-blind, parallel-group, randomized controlled intervention study of the effects vitamin D on alveolar macrophage gene expression in both smoking and nonsmoking subjects
For the purposes of this analysis, we excluded 27 subjects who smoked from the analysis, as smoking has known profound effects on macrophage gene expression
Summary
Vitamin D deficiency has been implicated as a factor in a number of infectious and inflammatory lung diseases. Alveolar macrophages play a key role in inflammation and defense of infection, but there are little data exploring the immunomodulatory effects of vitamin D on innate lung immunity in humans. Prior studies have indicated that vitamin D plays an important intracrine role in serum monocyte and macrophage response to infection [6]. Macrophages constitutively express the vitamin D receptor and serum macrophages have been shown to enhance innate immunity by vitamin D regulated production of cathelicidin in response to mycobacteria [7]. Vitamin D-regulated human cathelicidin production promotes autophagy of the macrophage, an important process in removing infectious antigens [8]
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