Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial

Abstract

BackgroundVitamin 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.MethodsWe 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.ResultsFifty-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.ConclusionsAlthough 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 registrationClinicalTrials.org: NCT01967628.

Vitamin D Deficiency Does Not Result in a Breach of Host Defense in Murine Models of Pneumonia

“…VitD derivatives are able to decrease the release of inflammatory cytokines from macrophages, neutrophils, and epithelial cells (32)(33)(34)(35)(36). In a hamster model, the application of VitD leads to reduced neutrophil recruitment and blunted inflammation (32,37).…”

Effect of vitamin D3on the antimicrobial activity of human airway surface liquid: preliminary results of a randomised placebo-controlled double-blind trial

“…This study design has been previously published. 27 Briefly, this is a single-centre, community-based, randomised, placebo-controlled double-blind trial. This pilot study investigated the effects of vitamin D 3 supplementation on the innate immunity of the lung.…”

“…Thereafter, a bronchoscopy was performed at the University of Iowa Hospitals and Clinics (Iowa City, Iowa, USA) as previously described. 27 To collect the ASL, three sponges were placed, one at a time, on the right main stem bronchus or bronchus intermedius for 30 s and then eluted with 1 mL of isotonic saline into a 1.5 mL tube. The tube was vortexed for 1 min and the sponges removed.…”

“…RNA preparation, quality analysis and microarray analysis were done as previously described. 28 Measurements of genome-wide macrophage messenger RNA expression and analysis were done as previously described 27 (Gene Expression Omnibus (GEO) accession # GSE56583).…”

“…To test this hypothesis, we investigated the antimicrobial activity of biobanked ASL samples collected through bronchoscopy of a cohort of smoking and non-smoking participants that randomly received either 1000 international units (IU) of vitamin D 3 /day or matching placebo for 90 days. 27 We also investigated the effect of smoking in the airway response to vitamin D 3 in vivo and in vitro.…”