Features of the IL6 gene expression under its experimental modification in vitro by vaccine antigens (SARS-CoV-2 and influenza virus) and benz(a)pyrene (using the IL6 transcript hs00174131_m1 as an example)

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Abstract

Introduction. Conditions under which the environment becomes destabilized allow hypothesizing about their modifying effects on the course of the SARS-CoV-2 infection and influenza. This determines the relevance of assessing the effects produced by these viral agents as well as environmental factors (for example, benz(a)pyrene), which use transcripts of candidate genes as a biological substrate, and expected effects in particular include specific expression of mRNA fragments.Materials and methods. The relative normalized level of gene (protein) expression of the IL6 hs00174131_m1 gene was assessed in incubation of a whole blood cell cultures with benz(a)pyrene, SARS-CoV-2 virus vaccine antigen and influenza virus vaccine antigens the assessment was performed on spontaneous and antigen incubation-induced experimental models in vitro for various polymorphism scenarios of the IL6 C(-174)G (rs1800795) gene.Results. Effects of bioexposition differed in the expression vector of mRNA fragments depending on polymorphic variants of the IL6 C(-174)G (rs1800795) gene. Thus, the minor variant of the IL6 C(-174)G gene polymorphism, was associated with activation of the expression of the IL6 hs00174131_m1 transcript (by 1.9 times). Exposure to viral antigens and benz(a)pyrene caused inhibition of the mRNA expression of the IL6 transcript hs00174131_m1 (by 1.2–3.7 times) for typical homozygous and heterozygous variants of the IL6 gene (rs1800795), which verifies occurrence of immunosuppression scenarios associated with the cytokine profile under antigenic exposure at the transcriptome level and allows clarifying the mechanism of modification of spontaneous effects by environmental chemical and biological factors depending on a Single Nucleotide Polymorphism (SNP).Research limitations. Are related to the limited sample.Conclusion. The hypothesis on modifying (inhibiting) effects of benz(a)pyrene and vaccine antigens (SARS-CoV-2 and influenza virus) on the IL6 C(-174)G (rs1800795) gene expression has been confirmed by using experimental in vitro models. These effects reflect intensity of induction of the scaled values of its IL6 hs00174131_m1 transcript, which makes it possible to clarify some pathways of immune disorders in the “genome-postgenome” system associated with the course of viral infections and to recommend the proposed sensitivity and effect markers as indicators for diagnosing and preventing COVID-19 and influenza in a destabilized environment (using benzo(a)pyrene as an example).Compliance with ethical standards. The study was approved by the Ethics Committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies (Protocol No. 13 dated of March 14, 2023). All patients were informed about the purpose of the study and gave informed voluntary consent to participate in the study.Contribution of the authors: Zaitseva N.V. — study design, editing; Otavina E.A. — data collection and analysis, statistical analysis, writing and editing the text; Dolgikh O.V. — study concept and design, editing the text; Kazakova O.A. — data collection and analysis, statistical analysis, editing the text; Starkova K.G. — statistical analysis, editing the text. All authors are responsible for approving the final version of the article and the integrity of its all parts.Funding. The study had no sponsorship.Conflict of interests. The authors declare no obvious or potential conflicts of interest in connection with the publication of this article.Received: March 11, 2025 / Accepted: June 24, 2025 / Published October 31, 2025

About the authors

Nina V. Zaitseva

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: znv@fcrisk.ru
ORCID iD: 0000-0003-2356-1145

Elena A. Otavina

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: eleninca@mail.ru
ORCID iD: 0000-0002-6173-6017

Oleg V. Dolgikh

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: oleg@fcrisk.ru
ORCID iD: 0000-0003-4860-3145

Olga A. Kazakova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: chakina2011@yandex.ru
ORCID iD: 0000-0002-0114-3930

Kseniya G. Starkova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: skg@fcrisk.ru
ORCID iD: 0000-0002-5162-9234

References

  1. Поздняков М.В., Мазилов С.И., Райкова С.В., Гусев Ю.С., Комлева Н.Е., Микеров А.Н. Оценка качества атмосферного воздуха в разных странах (обзор). Экология человека. 2023; 30(5): 325–39. https://doi.org/10.17816/humeco456406 https://elibrary.ru/vjistf
  2. Зайцева Н.В., Май И.В., Рейс Ж., Спенсер П., Кирьянов Д.А., Камалтдинов М.Р. К оценке дополнительной заболеваемости населения Covid-19 в условиях загрязнения атмосферного воздуха: методические подходы и некоторые практические результаты. Анализ риска здоровью. 2021; (3): 14–28. https://doi.org/10.21668/health.risk/2021.3.02 https://elibrary.ru/ulmefu
  3. Bukowska B., Mokra K., Michałowicz J. Benzopyrene-environmental occurrence, human exposure, and mechanisms of toxicity. Int. J. Mol. Sci. 2022; 23(11): 6348. https://doi.org/10.3390/ijms23116348
  4. Mathers C., Stevens G., Hogan D., Mahanani W.R., Ho J. Chapter 4. Global and regional causes of death: patterns and trends, 2000–15. In: Jamison D.T., Gelband H., Horton S., Jha P., Laxminarayan R., Mock C.N., et al. Disease Control Priorities: Improving Health and Reducing Poverty. 3rd ed. Washington: The International Bank for Reconstruction and Development, The World Bank; 2017. https://doi.org/10.1596/978-1-4648-0527-1_ch4
  5. Соленова Л.Г. Современные подходы к оценке влияния загрязнения окружающей среды на онкологический риск. Успехи молекулярной онкологии. 2020; 7(1): 17–22. https://doi.org/10.17650/2313-805X-2020-7-1-17-22 https://elibrary.ru/hixkbp
  6. Kalfaoglu B., Almeida-Santos J., Tye C.A., Satou Y., Ono M. T-cell dysregulation in COVID-19. Biochem. Biophys. Res. Commun. 2021; 538: 204–10. https://doi.org/10.1016/j.bbrc.2020.10.079
  7. Насонов Е.Л. Коронавирусная болезнь-2019 (COVID-19): значение ингибиторов IL-6. Пульмонология. 2020; 30(5): 629–44. https://doi.org/10.18093/0869-0189-2020-30-5-629-644 https://elibrary.ru/xemctk
  8. McGonagle D., Sharif K., O’Regan A., Bridgewood C. The role of cytokines including interleukin-6 in COVID-19 induced pneumonia and macrophage activation syndrome-like disease. Autoimmun. Rev. 2020; 19(6): 102537. https://doi.org/10.1016/j.autrev.2020.102537
  9. Ren J., Wang X.Q., Nakao T., Libby P., Shi G.P. Differential roles of interleukin-6 in severe acute respiratory syndrome-coronavirus-2 infection and cardiometabolic diseases. Cardiol. Discov. 2023; 3(3): 166–82. https://doi.org/10.1097/CD9.0000000000000096
  10. Abbasifard M., Khorramdelazad H. The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci. 2020; 257: 118097. https://doi.org/10.1016/j.lfs.2020.118097
  11. Ghazy A.A. Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome. J. Infect. Dev. Ctries. 2023; 17(3): 327–34. https://doi.org/10.3855/jidc.17717
  12. Azmi A., Rismani M., Pourmontaseri H., Mirzaii E., Niknia S., Miladpour B. The role of vitamin D receptor and IL-6 in COVID-19. Mol. Genet. Genomic. Med. 2023; 11(7): e2172. https://doi.org/10.1002/mgg3.2172
  13. Gou X., Yuan J., Wang H., Wang X., Xiao J., Chen J., et al. IL-6 During influenza-streptococcus pneumonia co-infected pneumonia — a protector. Front. Immunol. 2020; 10: 3102. https://doi.org/10.3389/fimmu.2019.03102
  14. Белушкина Н.Н., Чемезов А.С., Пальцев М.А. Генетические исследования мультифакториальных заболеваний в концепции персонализированной медицины. Профилактическая медицина. 2019; 22(3): 26–30. https://doi.org/10.17116/profmed20192203126 https://elibrary.ru/nsneag
  15. Тийс Р.П., Осипова Л.П. Интерлейкин-6: его роль в организме, генетический полиморфизм и значение при некоторых заболеваниях (литературный обзор). Медицинская генетика. 2022; 21(1): 14–27. https://doi.org/10.25557/2073-7998.2022.01.14-27 https://elibrary.ru/wvcnmu
  16. Verma S., Verma S., Khan F.H., Siddiqi Z., Raza S.T., Abbas M., et al. Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity. Int. J. Immunogenet. 2023; 50(1): 5–11. https://doi.org/10.1111/iji.12605
  17. Артемьева О.В., Ганковская Л.В. Роль полиморфных вариантов генов врожденного иммунитета в долголетии и возраст-ассоциированных заболеваниях. Иммунология. 2022; 43(3): 333–42. https://doi.org/10.33029/0206-4952-2022-43-3-333-342 https://elibrary.ru/aantmy
  18. Gubernatorova E.O., Gorshkova E.A., Polinova A.I., Drutskaya M.S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020; 53: 13–24. https://doi.org/10.1016/j.cytogfr.2020.05.009
  19. Mehta P., McAuley D.F., Brown M., Sanchez E., Tattersall R.S., Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020; 395(10229): 1033–4. https://doi.org/10.1016/S0140-6736(20)30628-0
  20. Табиханова Л.Э., Осипова Л.П., Чуркина Т.В., Ковалев С.С., Филипенко М.Л., Воронина Е.Н. Повышенные частоты аллелей ‒174G и ‒572C гена IL6 в популяциях коренных народов Сибири по сравнению с русскими. Молекулярная биология. 2023; 57(2): 350–9. https://doi.org/10.31857/S0026898423020210 https://elibrary.ru/eeihat

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