LATE-BREAKING ABSTRACT: Effect of vitamin D on inflammatory and antibacterial responses to cigarette smoke

Abstract

Background: Vitamin (vitD) deficiency has been associated with increased risk at COPD exacerbations and 2 RCTs showed that vitD supplementation reduces exacerbations in patients with vitD deficiency. In this study, we aimed to further investigate how vitD could influence COPD exacerbations by exploring effects on inflammation and bacterial clearance in response to cigarette smoke (CS). Methods: Human THP-1 macrophages were stimulated with cigarette smoke extract (CSE) and/or the active form of vitD (1,25(OH) 2 D). The release of inflammatory mediators as well as phagocytosis and oxidative burst were determined. VitD deficient or control mice were exposed to CS or ambient air for 6 weeks, followed by infection with nontypeable Haemophilus influenzae (NTHi). Bacterial loads and phagocytosis by inflammatory cells in the BAL fluid were assessed 16, 40 and 64h post-infection. Results: Post-treatment with 1,25(OH) 2 D significantly reduced the release of IL-8, TNF-α and MCP-1 by THP-1 macrophages compared to treatment with CSE alone. The CSE-induced defect in the phagocytic bacterial uptake and killing by oxidative burst was not affected by 1,25(OH) 2 D. Smoking also resulted in an impaired phagocytosis capacity of alveolar macrophages and neutrophils obtained from the BAL fluid of mice, which was not affected by long-term vitD deficiency in vivo . Surprisingly, bacterial loads were significantly lower in the vitD deficient mice compared to control mice 16, 40 and 64h post-infection, irrespective of CS exposure and phagocytosis capacity. Conclusion: Our results suggest that the beneficial effect of vitD on COPD exacerbations may not be mediated by bacterial killing, but by inhibitory effects on airway inflammation.