Features of cytokine expression under its modification with vaccine viral antigens (SARS-CoV-2 and Influenzavirus) and benzo(a)pyrene in experimental models in vitro

Introduction. In this study, we estimated features of modifying effects produced by benzo(a)pyrene well as by vaccine antigens of the SARS-CoV-2 and Influenzavirus viruses on the cytokine profile indicators under experimental conditions in vitro.

Materials and methods. To assess the cytokine-producing function, there was studied a mixed population of immunocytes, which was cultured for 72 hours, followed by analyzing the cytokine profile by enzyme immunoassay. Benzo(a)pyrene and viral vaccine antigens S protein of SARS-CoV-2 and hemagglutinins of Influenzaviruses of types A and B were used as inducing factors (modifiers).

Results. For exposure to benzo(a)pyrene in vitro there was noted multidirectional modification of cytokine mediator production with activation of IL-8 expression and suppression of IL-6 production (p=0.003–0.047). Similar changes in cytokine expression persisted under combined load with SARS-CoV-2 and Influenzavirus viral antigens. SARS-CoV-2 antigens predominantly stimulated the expression of cytokines (IL-1β, IL-10 and IL-8), while activation of the cytokine profile by Influenzavirus antigens was limited by an increase in IL-8 expression with its maximum achieved under combined (SARS-CoV-2 + Influenzavirus) viral load (p=0.002–0.047). Simultaneous introduction of benzo(a)pyrene and viral antigens into the cell culture involved an increase in expression of pro-inflammatory cytokines IL-1β and TNF-α (p=0.004–0.038).

Limitations. The limitations of the in vitro methodological approach are associated with ambiguity as regards translation and extrapolation of the results and conclusions obtained using cellular and subcellular models to processes formed within a macroorganism.

Conclusion. The results of the study clarify and supplement the ideas about participation of cytokine compartments of intercellular interactions in development of immune and inflammatory processes associated with persisting SARS-CoV-2 and Influenzavirus and modifying effects of benzo(a)pyrene. This made it possible to verify features of combined effects produced by chemical and biological factors in experimental models in vitro (imbalance in expression of IL-8 and IL-6), to identify markers of their effects for evaluating effectiveness of measures aimed at preventing socially significant viral infections under destabilization of the environment.

Compliance with ethical standards. The study was carried out in accordance with the Helsinki Declaration of the World Medical Association (revised 2013) and the Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (1999), according to the principles of “Good Clinical Practice” (GOST R 52379–2005) and approved by the Local Ethics Committee of the Federal Scientific Center for Medical and Preventive Technologies for Public Health Risk Management (Protocol No. 12 dated 03/14/2023). All donors signed voluntary informed consent to participate in the study.

Contribution:
Zaitseva N.V. – study concept and design, editing the text, responsibility for the integrity of all parts of the manuscript;
Starkova K.G. – study concept and design, data collection and analysis, writing the text;
Dolgikh O.V. – study concept and design, editing the text, responsibility for the integrity of all parts of the manuscript;
Shirinkina A.S. – data collection and analysis.
All authors are responsible for the approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The study had no sponsorship.

Received: February 19, 2025 / Accepted: March 6, 2025 / Published: March 31, 2025