Cigarette smoke and e-cigarette aerosol extracts induce myelopoiesis and suppress inflammatory cytokine production.

Tobacco and nicotine use remain leading preventable drivers of cancer risk, and both combustible cigarettes and electronic nicotine devices perturb immune function and hematopoiesis. However, side-by-side comparisons of their effects across the hematopoietic hierarchy remain limited. Here, we evaluate the impact of cigarette smoke extract (CSE) and e-cigarette vapor extract (EVE) on inflammatory responses in mature myeloid cells and on hematopoietic stem and progenitor cell function using complementary in vitro and in vivo approaches. Using a standardized protocol applied across multiple macrophage models, including RAW264.7 cells, THP-1 macrophages, primary mouse bone marrow-derived macrophages, and human peripheral blood mononuclear cells, we found that CSE consistently suppressed LPS-induced TNF-α secretion in a dose-dependent manner, whereas EVE alone had minimal effect. CSE also induced foam cell formation in macrophages through a reactive oxygen species-dependent mechanism. Additionally, both CSE and EVE suppressed hematopoietic progenitor colony formation. To model real-world exposure patterns, we used a nose-only inhalation system to deliver combustible cigarette smoke followed by e-cigarette aerosol to mice. Sequential smoke and e-cigarette exposure increased platelet counts and myeloid cell frequency, effects not observed with smoking cessation alone. Myeloid skewing persisted through secondary transplantation, indicating durable, cell-intrinsic changes to the hematopoietic stem cell compartment. Together, these findings demonstrate that tobacco and e-cigarette exposures blunt innate immune responsiveness while driving lasting myeloid-biased hematopoiesis, with implications for infection susceptibility, cardiovascular disease, and hematologic malignancy risk.