Effects of Combustible Cigarettes and Heated Tobacco Products on Systemic Inflammatory Response in Patients with Chronic Inflammatory Diseases
Nikolina Kastratovic,
Natasa Zdravkovic,
Ivan Cekerevac,
Vanesa Sekerus,
Carl Randall Harrell,
Violeta Mladenovic,
Aleksandar Djukic,
Ana Volarevic,
Marija Brankovic,
Tijana Gmizic,
Marija Zdravkovic,
Jelica Bjekic-Macut,
Nebojsa Zdravkovic,
Valentin Djonov,
Vladislav Volarevic
Affiliations
Nikolina Kastratovic
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Natasa Zdravkovic
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Ivan Cekerevac
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Vanesa Sekerus
Institute for Pulmonary Diseases of Vojvodina, 4 Institutski Put, 21204 Novi Sad, Serbia
Carl Randall Harrell
Regenerative Processing Plant, LLC, 34176 US Highway 19 N, Palm Harbor, FL 34684, USA
Violeta Mladenovic
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Aleksandar Djukic
Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Ana Volarevic
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Marija Brankovic
Department of Gastroenterology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia
Tijana Gmizic
Department of Gastroenterology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia
Marija Zdravkovic
Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia
Jelica Bjekic-Macut
Department of Endocrinology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia
Nebojsa Zdravkovic
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Valentin Djonov
Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland
Vladislav Volarevic
Center for Research on Harmful Effects of Biological and Chemical Hazards, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia
Smoke derived from combustible cigarettes (CCs) contains numerous harmful chemicals that can impair the viability, proliferation, and activation of immune cells, affecting the progression of chronic inflammatory diseases. In order to avoid the detrimental effects of cigarette smoking, many CC users have replaced CCs with heated tobacco products (HTPs). Due to different methods of tobacco processing, CC-sourced smoke and HTP-derived aerosols contain different chemical constituents. With the exception of nicotine, HTP-sourced aerosols contain significantly lower amounts of harmful constituents than CC-derived smoke. Since HTP-dependent effects on immune-cell-driven inflammation are still unknown, herein we used flow cytometry analysis, intracellular staining, and an enzyme-linked immunosorbent assay to determine the impact of CCs and HTPs on systemic inflammatory response in patients suffering from ulcerative colitis (UC), diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Both CCs and HTPs significantly modulated cytokine production in circulating immune cells, affecting the systemic inflammatory response in COPD, DM, and UC patients. Compared to CCs, HTPs had weaker capacity to induce the synthesis of inflammatory cytokines (IFN-γ, IL-1β, IL-5, IL-6, IL-12, IL-23, IL-17, TNF-α), but more efficiently induced the production of immunosuppressive IL-10 and IL-35. Additionally, HTPs significantly enhanced the synthesis of pro-fibrotic TGF-β. The continuous use of CCs and HTPs aggravated immune-cell-driven systemic inflammation in COPD and DM patients, but not in UC patients, suggesting that the immunomodulatory effects of CC-derived smoke and HTP-sourced aerosols are disease-specific, and need to be determined for specific immune-cell-driven inflammatory diseases.
