<p>Nicotine-Free e-Cigarette Vapor Exposure Stimulates IL6 and Mucin Production in Human Primary Small Airway Epithelial Cells</p>

Abstract

Purpose: Electronic cigarettes (e-cigs) are relatively new devices that allow the user to inhale a heated and aerosolized solution. At present, little is known about their health effects in the human lung, particularly in the small airways (<2 mm in diameter), a key site of airway obstruction and destruction in chronic obstructive pulmonary disease and other acute and chronic lung conditions. The aim of this study was to investigate the effect of e-cigarettes on human distal airway inflammation and remodeling. Methods: We isolated primary small airway epithelial cells from donor lungs without known lung disease. Small airway epithelial cells were cultured at air-liquid interface and exposed to 15 puffs vapor obtained by heating a commercially available e-cigarette solution (e-vapor) with or without nicotine. After 24 hrs of e-vapor exposure, basolateral and apical media as well as cell lysates were collected to measure the pleiotropic cytokine interleukin 6 (IL6) and MUC5AC, one of the major components in mucus. Results: Unlike the nicotine-containing e-vapor, nicotine-free e-vapor significantly increased the amount of IL6, which was coupled with increased levels of intracellular MUC5AC protein. Importantly, a neutralizing IL6 antibody (vs an IgG isotype control) significantly inhibited the production of MUC5AC induced by nicotine-free e-vapor. Conclusion:Our results suggest that human small airway epithelial cells exposed to nicotine-free e-vapor increase the inflammatory response and mucin production, which may contribute to distal lung airflow limitation and airway obstruction.

The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent

“…Other studies indicate no changes in antioxidant response in epithelial cells exposed to menthol-and tobacco-flavoured e-cigarette vapours [11,54].…”

“…No change in pro-inflammatory mediator secretion following tobacco-or grape-flavoured e-liquid exposure of human airway epithelial cells (H292) was reported [19]. Other studies showed increased IL-6 production with tobacco-flavoured liquid [52,54]. Exposure to cinnamon-flavoured e-liquid increases IL-8 and reactive oxygen species production by human fetal lung fibroblasts [19].…”

“…Exposure to 2,5-dimethypyrazine, the flavouring compound for chocolate flavour, alters ion conductance in immortalised human bronchial epithelial cells (16HBE14o-), a phenomenon attributed to protein kinase A-dependent activation of the cystic fibrosis transmembrane conductance regulator ion channel [53]. While tobacco-flavoured e-cigarette vapour does not change barrier electrical resistance in primary human small airway epithelial cells [54], cinnamaldehyde exposure decreases ciliary beat frequency in a dose-dependent manner in human bronchial epithelial cells [55].…”

“…Highly concentrated nicotine tobacco-and menthol-flavoured e-cigarette vapours also decreases epithelial cell barrier integrity [78]. Inhibition of Rho kinase and the addition of the sphingosine-1 Electronic cigarette vapour exposure Air-liquid interface [11,12,16,17,19,21,28,34,54,55,65,66,71,73,74,77,78,103] E-liquid mixed with cell medium or electronic cigarette vapour extracts [13-15, 18, 20, 22, 47, 50-53, 56-58, 70, 72, 75, 76, 79, 81, 104]…”

Cardiorespiratory and Immunologic Effects of Electronic Cigarettes

“…In view of these reports, it seems that e-liquids or extracts of e-cigarette aerosols activate both immune and non-immune cells, and the resultant changes in the production of immunomodulating cytokines may result in the development of a pro-inflammatory state in the lung. The development of an inflammatory state may also extend to other tissues and organs as diverse as nasal epithelial cells [ 86 ], cerebral cortex [ 87 ], and primary small airway epithelial cells [ 88 ]. Nevertheless, whether this inflammation is in the causal pathway that contributes to heightened disease risk of e-cigarette use remains unclear.…”