Vaping induces a marked pro-inflammatory state within the lung, which is at least partially due to its immunomodulatory effects

Jeffrey G. ShipmanKimberly MundyRob OnyenwokeVijay Sivaraman^*

• North Carolina Central University, Durham, United States

E-cigarette use or "vaping" exposes the lungs to a large array of chemicals, flavors and nicotine. Initially marketed as a healthier alternative to tobacco use, research has since begun to demonstrate vaping plays a role in immune dysfunction and inflammation, with both similarities and differences in effects observed compared with tobacco use. One potential mechanism of immune dysfunction is related to the regulation of monocyte-derived suppressor cells (MDSCs). MDSCs are a heterogenous population of cells that are generated and expand during inflammation and infection and are known and are commonly described as having immunosuppressive roles. MDSCs play an important role in modulating and suppressing immune response. However, vaping exposure may, in part, be associated with modifications in MDSC populations and inflammatory processes. Thus, we questioned whether vaping modulates MDSCs, potentially resulting in alterations in inflammatory cells and mediators in vivo. Briefly, male and female mice were vaped with JUUL Menthol (3% nicotine) pods using the SCIREQ InExpose system for 4 weeks. After 4 weeks, the mice were then exposed to lipopolysaccharide (LPS) to mimic a bacterial infection. Post-infection (24 hours) the mice were sacrificed, and bronchoalveolar lavage fluid (BALF) was collected. Vaped mice that were challenged with LPS demonstrated a decrease in macrophage numbers and significantly lower levels of granulocytic/ polymorphonuclear myeloid-derived (PMN) -MDSC compared to mice treated with LPS alone or only vaped. In contrast, monocytic (M) -MDSC numbers increased in the vaped and LPS challenged mice compared to the mice only treated with LPS in females while in males exhibited a decrease in vape+LPS groups compared to LPS alone. When comparing these results to the inflammatory data, several cytokines and chemokines linked to M-MDSC development and function were expressed after only LPS treatment but not by the dual vape+LPS treatment. However, exceptions were IFN-γ and RANTES/CCL5, which were increased after the dual treatment. These data suggest that the variation in cytokine and chemokine levels is associated with changes in M-MDSC populations.