The Synergistic Role of Il-6 And IL-17 In the Protection Against Seasonal Influenza in Iraqi Population
Keywords:
Seasonal influenza, cytokine response, IL-6 and IL-17, H3N2Abstract
Seasonal influenza remains an important public health problem around the world. There are inadequate reports from Iraq about the immunological profile and viral subtypes associated with it. Cytokines, more specifically interleukin-6 (IL-6) and Interleukin-17 (IL-17), are known to play a major role in antiviral immune responses. The study aims to measure serum levels of IL-6 and IL-17 in patients diagnosed with SI against healthy control individuals, to compare them relative to vaccination status and viral subtypes as well as their correlation with each other. This study was done at the Central Laboratory of General Hospital in Hilla City from October 2024 up to February 2025. There were sixty-six patients SI and 34 controls aged between 22-56 years who participated in the study. Serological testing helped identify viral subtypes (H1N1, H3N2) while cytokine levels were established through ELISA. Vaccination status as well as demographic data were captured. IL-6 and IL-17 levels were significantly higher in patients than in the controls (p<0.001). Vaccinated patients had lower IL-6 levels (p=0.04). H3N2 was the most common subtype (91%). There is a moderate positive correlation between IL-6 and IL-17 levels, r=0.398, p=0.004. This Iraqi cohort of SI patients demonstrated raised levels of IL-6 and IL-17, particularly in infection with H3N2. This emphasizes the immunological influence of seasonal influenza and protective modulation of cytokines by vaccination.
References
Al Saadi, M. A., Hussein, S. A., Alwan, A. A., & Jassim, M. A. (2023). Prevalence and Molecular Characterization of Influenza Virus in Iraq During the 2022–2023 Season. Journal of Infection in Developing Countries, 17(4), 379–387.
Al-Muhanna, M. A., Al-Dulaimi, D. A., & Saeed, S. M. (2023). Surveillance of influenza-like illness in Iraq: Challenges and opportunities. Iraqi Journal of Community Medicine, 36(1), 24–30.
Aufi, I. M., Khudhair, A. M., Ghaeb Al Saadi, L., Almoneem Ahmed, M. A., & Mahdi Shukur, F. M. (2021). Epidemiology and molecular characterization of seasonal influenza viruses in Iraq. Archives of Razi Institute, 76(4), 871–877.
Aufi, I. M., Khudhair, A. M., Ghaeb Al Saadi, L., Almoneem Ahmed, M. A., & Mahdi Shukur, F. M. (2020). Epidemiology of seasonal influenza outbreak among Iraqi population: 2018. Iraqi Journal of Agricultural Sciences, 51(1), 454–461.
Crowe, C. R., Chen, K., Pociask, D. A., Alcorn, J. F., Krivich, C., Enelow, R. I., ... & Kolls, J. K. (2009). Critical role of IL-17RA in immunopathology of influenza infection. Journal of Immunology, 183(8), 5301–5310.
de Jong, M. D., Simmons, C. P., Thanh, T. T., Hien, V. M., Smith, G. J., Chau, T. N., ... & Farrar, J. (2006). Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nature Medicine, 12(10), 1203–1207.
Dienz, O., Rud, J. G., Eaton, S. M., Lanthier, P. A., Burg, E., Drew, A., ... & Rincon, M. (2012). Essential role of IL-6 in protection against H1N1 influenza virus by promoting neutrophil survival in the lung. Journal of Immunology, 188(2), 842–850.
Dong, C. (2008). TH17 cells in development: An updated view of their molecular identity and genetic programming. Nature Reviews Immunology, 8(5), 337–348.
Gaffen, S. L. (2009). Structure and signalling in the IL-17 receptor family. Nature Reviews Immunology, 9(8), 556–567.
Goka, E. A., Vallely, P. J., Mutton, K. J., & Klapper, P. E. (2014). Influenza A viruses: Molecular pathology, epidemiology, and clinical implications. Pathology Research International, 2014, 562198. https://doi.org/10.1155/2014/562198
Iuliano, A. D., Roguski, K. M., Chang, H. H., Muscatello, D. J., Palekar, R., Tempia, S., ... & Bresee, J. S. (2018). Estimates of global seasonal influenza-associated respiratory mortality. The Lancet, 391(10127), 1285–1300.
Khaleel, H. A., Alhilfi, R. A., Rawaf, S., & Tabche, C. (2023). Identify future epidemic threshold and intensity for influenza like illness in Iraq by using the moving epidemic method. IJID Regions, 10, 126–131.
Kimura, A., & Kishimoto, T. (2010). IL-6: Regulator of Treg/Th17 balance. European Journal of Immunology, 40(7), 1830–1835.
Krammer, F., Smith, G. J. D., Fouchier, R. A. M., Peiris, M., Kedzierska, K., Doherty, P. C., ... & Palese, P. (2018). Influenza. Nature Reviews Disease Primers, 4, 3. https://doi.org/10.1038/s41572-018-0002-y
Lauder, S. N., Jones, E., Smart, K., Bloom, A., Williams, A. S., Hindley, J. P., ... & Gwinn, W. M. (2013). Interleukin-6 in the context of viral infection: Protective or detrimental? Journal of Clinical Immunology, 33(1), 30–37. https://doi.org/10.1007/s10875-012-9764-x
Li, C., Yang, P., Sun, Y., Wu, H., Zhang, H., Wang, Q., ... & Wang, C. (2012). IL-17A promotes virus replication in influenza virus-infected mice. Journal of Immunology, 189(4), 1929–1935.
Paget, J., Spreeuwenberg, P., Charu, V., Taylor, R. J., Iuliano, A. D., Bresee, J., ... & Viboud, C. (2019). Global mortality associated with seasonal influenza epidemics. Journal of Global Health, 9(2), 020421.
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295.
Tisoncik, J. R., Korth, M. J., Simmons, C. P., Farrar, J., Martin, T. R., & Katze, M. G. (2012). Into the eye of the cytokine storm. Microbiology and Molecular Biology Reviews, 76(1), 16–32.
To, K. K., Hung, I. F., Li, I. W., Lee, K. L., Koo, C. K., Yan, W. W., ... & Yuen, K. Y. (2010). Delayed viral clearance and cytokine activation in severe pandemic H1N1 influenza. Clinical Infectious Diseases, 50(6), 850–859.
van de Sandt, C. E., Kreijtz, J. H., & Rimmelzwaan, G. F. (2021). Efficacy of seasonal influenza vaccination in elderly populations. Drugs & Aging, 38, 411–424.
World Health Organization – Eastern Mediterranean Regional Office. (2023). Influenza surveillance bulletin, Eastern Mediterranean Region. Retrieved from https://www.emro.who.int.
