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Abstract
Introduction Vitamin D3 supplementation has been reported to prevent lung infections and increase the gene expression of antimicrobial peptides such as cathelicidin. We investigated the effect of vitamin D3 supplementation on the antimicrobial activity of airway surface liquid (ASL) in human subjects. Since smoking can increase the risk of respiratory infections, we also investigated the effect of smoking in the cathelicidin response to vitamin D3 in human airway epithelia in vitro.
Methods This study is a subanalysis of single-centre community-based randomised placebo-controlled double-blind trial. Participants were randomised to receive 1000 international units per day of oral vitamin D3 or identical placebo for 90 days. Blood and ASL samples were collected preintervention and postintervention. 105 participants were originally enrolled, 86 completed the trial, and due to low protein concentration in the samples, 40 participants were finally analysed. Our primary outcome was ASL antimicrobial activity. We also considered secondary outcomes including changes in serum concentration of 25-hydroxyvitamin D3 (25(OH)D3), 1,25-hydroxyvitamin D3, calcium and parathyroid hormone (PTH). In addition, we studied the effect of cigarette smoke extract (CSE) exposure to primary human airway epithelial cell cultures on the gene expression of cathelicidin in response to vitamin D3 and expression of CYP27B1 (1-alpha hydroxylase), responsible for vitamin D3 activation.
Results Vitamin D3 supplementation significantly increased both ASL antimicrobial activity and serum concentration of 25(OH)D3. In a subgroup analysis, we found that smokers did not increase their baseline antimicrobial activity in response to vitamin D3. Exposure to CSE on human airway epithelia decreased baseline CYP27B1 gene expression and cathelicidin response to 25(OH)D3.
Conclusion Vitamin D3 supplementation for 90 days increases ASL antimicrobial activity. Data from this preliminary study suggest that smoking may alter the ability of airway epithelia to activate vitamin D3 and increase the gene expression of cathelicidin antimicrobial peptide.
Trial registration number NCT01967628; Post-results.
- Airway Epithelium
- Innate Immunity
- Bacterial Infection
- Respiratory Infection
- Tobacco and the lung
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Footnotes
Contributors Conception and design: APC, AKG, LGVB, JZ. Performing the experiments: LGVB, MC, OGVC, AAP. Analysis and interpretation: LGVB, APC, AKG, JZ. Drafting the manuscript for important intellectual content: LGVB, APC, AKG, JZ.
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval IRB# 200607708.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Microarray analysis of alveolar macrophages is available to anybody by accessing Gene Expression Omnibus (GEO) accession number: GSE56583. In addition, anybody can contact either corresponding authors, Alicia Gerke at alicia-gerke@uiowa.edu or Alejandro Comellas at alejandro-comellas@uiowa.edu for any enquiries about the manuscript or data reported.