Effects of Combustible Cigarettes and Heated Tobacco Products on Systemic Inflammatory Response in Patients with Chronic Inflammatory Diseases

Author:

Kastratovic Nikolina12ORCID,Zdravkovic Natasa134,Cekerevac Ivan135ORCID,Sekerus Vanesa67,Harrell Carl Randall8ORCID,Mladenovic Violeta34,Djukic Aleksandar34,Volarevic Ana19,Brankovic Marija1011ORCID,Gmizic Tijana1011ORCID,Zdravkovic Marija1112ORCID,Bjekic-Macut Jelica13,Zdravkovic Nebojsa114ORCID,Djonov Valentin15,Volarevic Vladislav121617ORCID

Affiliation:

1. 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

2. Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia

3. Department of Internal Medicine, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia

4. Center for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia

5. Pulmonology Clinic, University Clinical Center Kragujevac, 30 Zmaj Jovina Street, 34000 Kragujevac, Serbia

6. Institute for Pulmonary Diseases of Vojvodina, 4 Institutski Put, 21204 Novi Sad, Serbia

7. Department of Biochemistry, Faculty of Medicine, University of Novi Sad, 3 Hajduk Veljkova Street, 21000 Novi Sad, Serbia

8. Regenerative Processing Plant, LLC, 34176 US Highway 19 N, Palm Harbor, FL 34684, USA

9. Department of Psychology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia

10. Department of Gastroenterology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia

11. Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia

12. Department of Cardiology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia

13. Department of Endocrinology, University Medical Center “Bežanijska Kosa”, Dr Zoza Matea bb, 11080 Belgrade, Serbia

14. Department of Statistics, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia

15. Institute of Anatomy, University of Bern, Baltzerstrasse 2, 3012 Bern, Switzerland

16. Department of Microbiology and Immunology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, 34000 Kragujevac, Serbia

17. Faculty of Pharmacy Novi Sad, Trg Mladenaca 5, 21000 Novi Sad, Serbia

Abstract

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.

Funder

Foundation for a Smoke-Free World, Inc.

PMI Global Services Inc.

Ministry of Science Republic of Serbia

Faculty of Medical Sciences University of Kragujevac

Publisher

MDPI AG

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