The role of Interleukin-6 (IL-6) in pathogensis of COVID -19


  • Noorulhuda F. Khalaf Tropical Biological Research Unit, College of Science/University of Baghdad
  • Sinai W. Mohammed University of Baghdad, College of Science, Tropical Biological Research Unit
  • Ahmed Y. Hanoon Tropical Biological Research Unit, College of Science/University of Baghdad



COVID-19, Cytokines, IL-6, Pathogenesis


Dissimilar to all other pandemics in the past five decades, the humanity has been ravaged by the coronavirus disease COVID-19. Starting from its outbreak, the disease's understanding has advanced quickly; multi-organ involvement is the key factor affecting the prognosis of the disease. Mortality and morbidity are closely related to acute respiratory distress syndrome, renal failure, cardiac failure, liver damage, multi-organ failure, and shock. In the initial phases of viral infection, detecting and controlling pro-inflammatory responses are essential. Throughout patient monitoring, it's crucial to consider the COVID-19 treatment's unknowable response. It has been discovered that IL-6 is causally linked to greater mortality. It is a reliable indicator regarding the progression of clinical profile as well as the prognosis of the disease. A highly important cytokine, after the activated macrophages, is it. As a result, a measure for COVID-19 could be the control regarding systemic IL-6 levels in the individuals that have been infected by SARS-CoV-2. This study has demonstrated the significance of IL-6 in COVID-19's immunopathology


1. Sharma, A., Farouk, I. A., & Lal, S. K. (2021). COVID-19?: A Review on the Novel Coronavirus Disease. Viruses, 13(2), 1–25.
2. Fehr, A. R., & Perlman, S. (2015). Coronaviruses: An Overview of Their Replication and Pathogenesis. In H. J. Maier, E. Bickerton, & P. Britton (Eds.), Coronaviruses: Methods and Protocols (pp. 1–23). Springer New York.
3. Chen, N., Zhou, M., Dong, X., Qu, J., Gong, F., Han, Y., Qiu, Y., Wang, J., Liu, Y., Wei, Y., Xia, J., Yu, T., Zhang, X., & Zhang, L. (2020). Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet, 395(10223), 507–513.
4. Jartti, L. (2011). New Respiratory Viruses and the Elderly. The Open Respiratory Medicine Journal, 5(1), 61–69.
5. WHO. (2020). Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases. WHO - Interim Guidance, 2019(January), 1–7.
6. Chan, J. F. W., Yuan, S., Kok, K. H., To, K. K. W., Chu, H., Yang, J., Xing, F., Liu, J., Yip, C. C. Y., Poon, R. W. S., Tsoi, H. W., Lo, S. K. F., Chan, K. H., Poon, V. K. M., Chan, W. M., Ip, J. D., Cai, J. P., Cheng, V. C. C., Chen, H., … Yuen, K. Y. (2020). A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet, 395(10223), 514–523.
7. Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., Manson, J. J., & HLH Across Speciality Collaboration, UK (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England), 395(10229), 1033–1034.
8. Lu, R., Zhao, X., Li, J., Niu, P., Yang, B., Wu, H., Wang, W., Song, H., Huang, B., Zhu, N., Bi, Y., Ma, X., Zhan, F., Wang, L., Hu, T., Zhou, H., Hu, Z., Zhou, W., Zhao, L., Chen, J., … Tan, W. (2020). Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet (London, England), 395(10224), 565–574.
9. Okabayashi T, Kariwa H, Yokota SI et al. Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections. J. Med. Virol. 78(4), 417–424 (2006).Crossref, Medline, CAS, Google Scholar
10. Wan S, Yi Q, Fan S et al. Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). MedRxiv doi:10.1101/2020.02.10.20021832 (2020) (Epub ahead of print).Medline, Google Scholar
11. Bahrami, A., & Ferns, G. A. (2020). Genetic and pathogenic characterization of SARS-CoV-2: A review. Future Virology, 15(8), 533–549.
12. Cao, W., & Li, T. (2020). COVID-19: towards understanding of pathogenesis. Cell Research, 30(5), 367–369.
13. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 39(5), 529–539 (2017).Crossref, Medline, CAS, Google Scholar
14. Wong CK, Lam CWK, Wu AKL et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome. Clin. Exp. Immunol. 136(1), 95–103 (2004).Crossref, Medline, CAS, Google Scholar
15. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395(10223), 497–506 (2020).Crossref, Medline, CAS, Google Scholar
16. 8-Diao B, Wang C, Tan Y et al. Reduction and functional exhaustion of T cells in patients with coronavirus disease 2019 (COVID-19). MedRxiv doi:10.1101/2020.02.18.20024364 (2020) (Epub ahead of print).Medline, Google Scholar
17. Lee DW, Gardner R, Porter DL et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124(2), 188–195 (2014).Crossref, Medline, CAS, Google Scholar
18. Heinrich PC, Castell JV, Andus T. Interleukin-6 and the acute phase response. Biochem. J. 265(3), 621–636 (1990).Crossref, Medline, CAS, Google Scholar
19. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int. Rev. Immunol. 30(1), 16–34 (2011).Crossref, Medline, CAS, Google Scholar
20. Narazaki M, Kishimoto T. The two-faced cytokine IL-6 in host defense and diseases. Int. J. Mol. Sci. 19(11), 3528 (2018).Crossref, Google Scholar
21. Qian S, Gao Z, Cao R et al. Transmissible gastroenteritis virus infection up-regulates FcRn expression via nucleocapsid protein and secretion of TGF-? in porcine intestinal epithelial cells. Front. Microbiol. 10, 3085 (2019).Crossref, Medline, Google Scholar
22. Ray A, Prefontaine KE. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc. Natl Acad. Sci. USA 91(2), 752–756 (1994).Crossref, Medline, CAS, Google Scholar
23. Delerive P, De Bosscher K, Besnard S et al. Peroxisome proliferator-activated receptor ? negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-?B and AP-1. J. Biol. Chem. 274(45), 32048–32054 (1999).Crossref, Medline, CAS, Google Scholar
24. Grupp SA, Kalos M, Barrett D et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N. Engl. J. Med. 368(16), 1509–1518 (2013).Crossref, Medline, CAS, Google Scholar
25. Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 6(10), a016295 (2014).Crossref, Medline, Google Scholar
26. Zheng J, Shi Y, Xiong L et al. The expression of IL-6, TNF-? and MCP-1 in respiratory viral infection in acute exacerbations of chronic obstructive pulmonary disease. J. Immunol. Res. 2017, 8539294 (2017).Crossref, Medline, Google Scholar
27. Velazquez-Salinas L, Verdugo-Rodriguez A, Rodriguez LL, Borca MV. The role of interleukin 6 during viral infections. Front. Microbiol. 10, 1057 (2019).Crossref, Medline, Google Scholar
28. Dholaria BR, Bachmeier CA, Locke F. Mechanisms and management of chimeric antigen receptor T-cell therapy-related toxicities. BioDrugs 33(1), 45–60 (2019).Crossref, Medline, CAS, Google Scholar
29. Ding C, Jones G: Technology evaluation: MRA, Chugai. Curr Opin Mol Ther. 2003 Feb;5(1):64-9.
30. Xu X, Han M, Li T et al. Effective treatment of severe COVID-19 patients with tocilizumab. Proc. Natl Acad. Sci. USA 117(20), 10970–10975 (2020).Crossref, Medline, CAS, Google Scholar
31. Lombardia SR. Vademecum per la cura delle persone con malattia da COVID-19. Scholar
32. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet 395(10223), 473–475 (2020).Crossref, Medline, CAS, Google Scholar




How to Cite

Noorulhuda F. Khalaf, W. Mohammed, S., & Ahmed Y. Hanoon. (2023). The role of Interleukin-6 (IL-6) in pathogensis of COVID -19. University of Thi-Qar Journal of Science, 10(1).