title: Effects of vitamin D supplementation on alveolar macrophage gene expression: preliminary results of a randomized, controlled trial.
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.
  
  
  BACKGROUND
  ClinicalTrials.org: NCT01967628.
authors.affiliation: Department of Internal Medicine, University of Iowa, 200 Hawkins Dr, Iowa City 52242, IA, USA. alicia-gerke@uiowa.edu.
authors.forename: Alicia K
authors.initials: AK
authors.lastname: Gerke
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Pezzulo
authors.forename: Fan
authors.initials: F
authors.lastname: Tang
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Cavanaugh
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Bair
authors.forename: Emily
authors.initials: E
authors.lastname: Phillips
authors.forename: Linda S
authors.initials: LS
authors.lastname: Powers
authors.forename: Martha M
authors.initials: MM
authors.lastname: Monick