Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model
ORCID
Ross: https://orcid.org/0000-0002-9167-8452; Kaplan: https://orcid.org/0000-0002-1992-4145
MSU Affiliation
College of Veterinary Medicine; Department of Comparative Biomedical Sciences; Department of Basic Sciences; Department of Pathobiology and Population Medicine; Center for Environmental Health Sciences
Creation Date
2026-03-02
Abstract
The use of electronic nicotine delivery systems (ENDS), also known as electronic-cigarettes (e-cigs), has raised serious public health concerns, especially in light of the 2019 outbreak of e-cig or vaping product use-associated acute lung injury (EVALI). While these cases have mostly been linked to ENDS that contain vitamin E acetate, there is limited research that has focused on the chronic pulmonary effects of the delivery vehicles (i.e., without nicotine and flavoring). Thus, we investigated lung function and immune responses in a mouse model following exposure to the nearly ubiquitous e-cig delivery vehicles, vegetable glycerin (VG) and propylene glycol (PG), used with a specific 70%/30% ratio, with or without vanilla flavoring. We hypothesized that mice exposed sub-acutely to these e-cig aerosols would exhibit lung inflammation and altered lung function. Adult female C57BL/6 mice (n = 11-12 per group) were exposed to filtered air, 70%/30% VG/PG, or 70%/30% VG/PG with a French vanilla flavoring for 2 h a day for 6 weeks. Prior to sacrifice, lung function was assessed. At sacrifice, broncho-alveolar lavage fluid and lung tissue were collected for lipid mediator analysis, flow cytometry, histopathology, and gene expression analyses. Exposures to VG/PG + vanilla e-cig aerosol increased lung tidal and minute volumes and tissue damping. Immunophenotyping of lung immune cells revealed an increased number of dendritic cells, CD4+ T cells, and CD19+ B cells in the VG/PG-exposed group compared to air, irrespective of the presence of vanilla flavoring. Quantification of bioactive lung lipids demonstrated a >3-fold increase of 2-arachidonoylglycerol (2-AG), an anti-inflammatory mediator, and a 2-fold increase of 12-hydroxyeicosatetraenoic acid (12-HETE), another inflammatory mediator, following VG/PG exposure, with or without vanilla flavoring. This suggests that e-cig aerosol vehicles may affect immunoregulatory molecules. We also found that the two e-cig aerosols dysregulated the expression of lung genes. Ingenuity Pathway Analysis revealed that the gene networks that are dysregulated by the VG/PG e-cig aerosol are associated with metabolism of cellular proteins and lipids. Overall, our findings demonstrate that VG and PG, the main constituents of e-liquid formulations, when aerosolized through an e-cig device, are not harmless to the lungs, since they disrupt immune homeostasis.
Publication Date
8-21-2020
Publication Title
International Journal of Molecular Sciences
Publisher
MDPI
First Page
1
Last Page
22
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Szafran, B. N., Pinkston, R., Perveen, Z., Ross, M. K., Morgan, T., Paulsen, D. B., Penn, A. L., Kaplan, B. L. F., & Noël, A. (2020). Electronic-Cigarette Vehicles and Flavoring Affect Lung Function and Immune Responses in a Murine Model. International Journal of Molecular Sciences, 21(17), 6022. https://doi.org/10.3390/ijms21176022
