Cigarette Smoke and E-Cigarette Aerosol Extracts Induce Myelopoiesis and Suppress Inflammatory Cytokine Production

ABSTRACT Tobacco and nicotine use remain the leading preventable drivers of cancer risk, and both direct and secondhand exposure to combustible cigarettes or electronic nicotine devices perturbs immune function and hematopoiesis. Here, we evaluate the impact of e-cigarette vapor and combustible cigarette smoke on in vitro cell inflammatory responses and in vivo long-term hematopoietic differentiation. In cell-based studies, cigarette smoke extract (CSE) and e-cigarette vapor extract (EVE) consistently suppress LPS-induced TNF-α secretion across macrophage/monocyte models, including primary mouse and human cells and complementary cell lines, indicating a reproducible immunosuppressive effect on mature myeloid cells. Brief ex vivo exposure to CSE also alters myeloid subset composition and modifies the proliferative behavior of Tet2-knockout cells, suggesting that smoke-related cues can reshape competitive dynamics among mutant and wild-type myeloid progenitors. To assess consequences of smoking behavior in vivo, we used a custom nose-cone inhalation system to deliver controlled exposures to combustible cigarette smoke or e-cigarette aerosol to mice. Chronic exposure increased myeloid proliferation, consistent with smoking behavior inducing premature aging of the hematopoietic stem cell pool. Thus, these studies support a model in which tobacco exposures blunt innate immune responsiveness while simultaneously driving myeloid expansion conditions that accelerate hematopoietic aging.