Dysregulated repair and inflammatory responses by e-cigarette-derived inhaled nicotine and humectant propylene glycol in a sex-dependent manner in mouse lung.

Introduction:
This article examines the effects of electronic cigarette (e-cig) aerosols containing nicotine and propylene glycol (PG) on lung inflammation and dysregulated repair responses in a sex-dependent manner. The study compares the effects of e-cig aerosols containing PG with and without nicotine on inflammatory cell counts, myeloperoxidase (MPO) levels, cytokine release, and gene expression of lipogenic/myogenic markers in mouse lungs. The study also investigates the effects of e-cig aerosols on pro-inflammatory cytokine release in human 3D in vitro models of Epiairway tissues.

Key Points:

* acute exposure to e-cig aerosols containing PG with nicotine showed increased inflammatory cell counts (neutrophils and CD8a+ T-lymphocyte influx) compared to PG and air control groups in a sex-dependent manner.
* PG alone exposure significantly increased MPO levels measured in BaLF, while PG and nicotine combination inhibited these levels.
* acute exposure to e-cig aerosol containing PG with nicotine caused a significant increase in several pro-inflammatory cytokines/chemokines compared to PG and air control groups in a sex-dependent manner.
* acute exposure of e-cig aerosols containing PG with or without nicotine increased protein abundance of naChRα3 and naChRα7 in mouse lungs, with more robust effects in females.
* Sex-dependent effects were observed in protein abundance of lipogenic and myogenic markers in mouse lung following acute e-cig exposure.
* Nicotine significantly downregulated IL-6 secretion by tissues from healthy subjects, while it increased by tissues from COPD subjects in human 3D Epiairway tissue models.
* PG with or without nicotine induced significant IL-8 release by both healthy and COPD donors compared to untreated controls.

Main Message:
The study suggests that acute exposure to e-cig aerosols containing PG with nicotine can induce lung inflammation and dysregulated repair responses in a sex-dependent manner. The findings highlight the importance of further studies to understand the exact mechanisms involved in e-cig aerosol-induced lung toxicity and the potential long-term consequences of e-cig use. The study also emphasizes the need for careful consideration of inhaled PG/VG or any oil (MCT) droplets-induced inflammatory pneumonitis in e-cig users presenting with respiratory symptoms.

Wang q, Khan Na, Muthumalage T, et al. Dysregulated repair and inflammatory responses by e-cigarette-derived inhaled nicotine and humectant propylene glycol in a sex-dependent manner in mouse lung. FaSEB bioadvances. 2019;1(10):609-623. doi:10.1096/fba.2019-00048