Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases.

Kastratovic, Nikolina; Cekerevac, Ivan; Sekerus, Vanesa; Markovic, Vladimir; Arsenijevic, Aleksandar; Volarevic, Ana; Harrell, Carl Randall; Jakovljevic, Vladimir; Djonov, Valentin; Volarevic, Vladislav (2024). Effects of combustible cigarettes and heated tobacco products on immune cell-driven inflammation in chronic obstructive respiratory diseases. (In Press). Toxicological sciences Oxford University Press 10.1093/toxsci/kfae068

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Since long-term effects of heated tobacco products (HTP) on the progression of chronic obstructive pulmonary disease (COPD) are unknown, we used COPD mice model to compare immune cell-dependent pathological changes in the lungs of animals which were exposed to HTP or combustible cigarettes (CCs). We also performed intracellular staining and flow cytometry analysis of immune cells which were present in the blood of CCs and HTP users who suffered from immune cell-driven chronic obstructive respiratory diseases. CCs enhanced NLRP3 inflammasome-dependent production of inflammatory cytokines in lung-infiltrated neutrophils and macrophages and increased influx of cytotoxic Th1, Th2 and Th17 lymphocytes in the lungs of COPD mice. Similarly, CCs promoted generation of inflammatory phenotype in circulating leukocytes of COPD patients. Opposite to CCs, HTP favored expansion of immunosuppressive, IL-10-producing, FoxP3-expressing T, NK and NKT cells in inflamed lungs of COPD mice. Compared to CCs, HTP had weaker capacity to promote synthesis of inflammatory cytokines in lung-infiltrated immune cells. Significantly lower number of inflammatory neutrophils, monocytes, Th1, Th2 and Th17 lymphocytes were observed in the blood of patients who consumed HTP than in the blood of CCs users, indicating different effects of CCs and HTP on immune cells' phenotype and function.

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