Immunological and toxicological risk assessment of e-cigarettes

Abstract

Knowledge of the long-term toxicological and immunological effects of e-cigarette (e-cig) aerosols remains elusive due to the relatively short existence of vaping. Therefore, we performed a systematic search of articles published in public databases and analysed the research evidence in order to provide critical information regarding e-cig safety. Electronic nicotine delivery systems (or e-cigs) are an alternative to traditional cigarettes for the delivery of nicotine and are typically filled with glycerol or propylene glycol-based solutions known as e-liquids. Though present in lower quantities, e-cig aerosols are known to contain many of the harmful chemicals found in tobacco smoke. However, due to the paucity of experimental data and contradictory evidence, it is difficult to draw conclusive outcomes regarding toxicological, immunological and clinical impacts of e-cig aerosols. Excessive vaping has been reported to induce inflammatory responses including mitogen-activated protein kinase, Janus tyrosine kinase/signal transducer and activator of transcription and nuclear factor-κB signalling, similar to that induced by tobacco smoke. Based on recent evidence, prolonged exposure to some constituents of e-cig aerosols might result in respiratory complications such as asthma, chronic obstructive pulmonary disease and inflammation. Future studies are warranted that focus on establishing correlations between e-cig types, generations and e-liquid flavours and immunological and toxicological profiles to broaden our understanding about the effects of vaping.

FIGURE 1

E-cigarette models. a) First generation; b) second generation; c) third generation; d) fourth generation.

FIGURE 2

Inflammatory responses elicited by e-liquid vaping. E-liquid vaping results in recruitment of immune cells to the site of exposure, i.e. nasal and throat epithelial cells. Tissue macrophages are among the first lines of defence activated by exposure to e-cigarette vapours. Activated macrophages participate in phagocytosis and release pro-inflammatory cytokines such as interleukin (IL)-6, IL-10, IL-1β, etc. a) In turn, these cytokines lead to B-cell and T-cell differentiation and participate in downstream signalling mechanisms. b) IL-6 mediated activation of the JAK–STAT (Janus tyrosine kinase/signal transducer and activator of transcription) pathway is one such downstream pathway that is known to be activated by the action of e-vapours. IL-6 production by exposure to e-vapours causes STAT3 phosphorylation which further elicits production of other cytokines and chemokines, and, most importantly promotes neutrophil adhesion and migration into the lungs. c) Neutrophil migration into the tissue results in release of neutrophil elastase and matrix metallopeptidase-9, which in turn causes tissue destruction in emphysematous lungs and chronic obstructive pulmonary disease. d) Furthermore, neutrophils release various cytokines and chemokines such as tumour necrosis factor (TNF)-α, IL-10 and IL-1β, which activate p38 and nuclear factor (NF)-кB mediated signalling pathways that might result in inflammation or apoptosis. e) Exposure to e-vapours further results in release of β-defensins by epithelial cells. β-defensins have antimicrobial actions and participate in eliciting an inflammatory response; however, production of the SPLUNC1 (short palate, lung and nasal epithelium clone 1) protein known to induce innate immunity in airway epithelial cells is lowered on exposure to e-vapours. ICAM: intercellular adhesion molecule.