Lymphocyte, IL-10, IL-6, and IFN-g Cytokines Modulation in SARS-CoV-2 Patients
Inaam Ali Abid 1*, Ismail Ibrahim Latif 2, Namer Fadhil Ghaab 3, Saad Ahmed Ali Jadoo 4
Journal of Angiotherapy 8(4) 1-8 https://doi.org/10.25163/angiotherapy.849584
Submitted: 05 March 2024 Revised: 02 April 2024 Published: 06 April 2024
The study showed gender disparities in COVID-19 severity, revealing elevated cytokine levels of IL-10, IL-6, and IFN-g in males, as a potential immune response variations.
Abstract
Background: The outbreak of Coronavirus Disease 2019 (COVID-19) shows significant challenges globally since its emergence in late 2019. With its arrival in Iraq in early 2020, understanding the disease's severity and its differential impact on various demographic groups became paramount. This study aimed to investigate the severity of COVID-19 infection among patients admitted to Baquba Teaching Hospital, Diyala Province, Iraq, focusing on gender disparities and their correlation with laboratory results, including serum levels of Interleukin-10 (IL-10), Interleukin-6 (IL-6), and Interferon-? (IFN-?). Methods: A cross-sectional study was conducted between September and December 2020, involving the collection of 172 human serum samples. These samples were divided into four groups: moderate, severe, critical, and control, with each group comprising forty-three samples. Results: Statistical analysis revealed a higher infection rate among males (65.9%) compared to females (34.1%). Lymphocyte levels exhibited a significant decrease in the male group (9.66 ± 0.57%) compared to the female group (11.55 ± 1.05%), with a p-value of 0.020. The level of IFN-? showed a significant increase in the female group (160.81 ± 16.19 pg/lm) compared to the male group (136.73 ± 14.93 pg/ml), with a p-value of 0.022. Furthermore, the levels of IL-10 and IL-6 significantly increased in the male group (247.70 ± 23.93 pg/ml and 39.24 ± 6.55 pg/ml, respectively) compared to the female group (174.75 ± 18.63 pg/ml and 18.55 ± 3.31 pg/ml, respectively), with p-values of 0.009 and 0.008, respectively. Conclusions: The study concludes that the rate of COVID-19 infection is higher in men than in women. Additionally, lymphocyte count decreased in all COVID-19 patients, particularly significantly in the male group compared to the female group. Moreover, levels of the cytokines IL-10, IL-6, and IFN-? were generally elevated in COVID-19 patients, with IL-10 and IL-6 significantly increased in the male group compared to the female group, while IFN-? showed a significant increase in the female group compared to the male group.
Keywords: IL-10, IL-6, IFN-?, COVID-19 severity, Gender differences, Cytokine levels, Lymphocyte count, Iraqi patients
References
Abdel-Hamed, E. F., Ibrahim, M. N., Mostafa, N. E., Moawad, H. S., Elgammal, N. E., Darwiesh, E. M., ... Hindawi, S. I. (2021). Role of interferon gamma in SARS-CoV-2-positive patients with parasitic infections. Gut Pathogens, 13(1), 29.
Aishath Thahuseen Waheed, Thurga Ayavoo, Karthikeyan Murugesan, Fouad Saleih R. AL-Suede, Ashok Gnanasekaran. (2021). Immunomodulatory Effect of Tinospora cordifolia with Special Reference to Suppression of Cytokine Storm Induced in SARS-CoV-2, Journal of Angiotherapy, 5(1), 218-225
Ambrosino, I., Barbagelata, E., Ortona, E., Ruggieri, A., Massiah, G., Giannico, O. V., ... Moretti, A. M. (2020). Gender differences in patients with COVID-19: A narrative review. Monaldi Archives for Chest Disease, 90(2).
Asselta, R., Paraboschi, E. M., Mantovani, A., & Duga, S. (2020). ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY), 12(11), 10087.
Baena, E., Shao, Z., Linn, D. E., Glass, K., Hamblen, M. J., Fujiwara, Y., ... Li, Z. (2013). ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients. Genes & Development, 27(6), 683-698.
Chen, R., Liang, W., Jiang, M., Guan, W., Zhan, C., Wang, T., ... for COVID, M. T. E. G. (2020). Risk factors of fatal outcome in hospitalized subjects with coronavirus disease 2019 from a nationwide analysis in China. Chest, 158(1), 97-105.
Cook, I. F. (2008). Sexual dimorphism of humoral immunity with human vaccines. Vaccine, 26(29-30), 3551-3555.
De Groot, N. G., & Bontrop, R. E. (2020). COVID-19 pandemic: Is a gender-defined dosage effect responsible for the high mortality rate among males?
Dhar, S. K., Vishnupriyan, K., Damodar, S., Gujar, S., & Das, M. (2021). IL-6 and IL-10 as predictors of disease severity in COVID-19 patients: Results from meta-analysis and regression. Heliyon, 7(2).
di Mauro, G., Scavone, C., Rafaniello, C., Rossi, F., & Capuano, A. (2020). SARS-Cov-2 infection: Response of human immune system and possible implications for the rapid test and treatment. International Immunopharmacology, 84, 106519.
Docherty, A. B., Harrison, E. M., Green, C. A., Hardwick, H. E., Pius, R., Norman, L., ... & Semple, M. G. (2020). Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ, 369.
Esra Hassan Abd Ali. (2024). Inflammatory Modulation of Interleukin-17 and -23 in Long COVID Diabetic Patients, Journal of Angiotherpay, 8(3), 1-7, 9583
Forsblom, E., Silen, S., Kortela, E., Ahava, M., Kreivi, H. R., Holmberg, V., ... & Meretoja, A. (2021). Male predominance in disease severity and mortality in a low Covid-19 epidemic and low case-fatality area–a population-based registry study. Infectious Diseases, 53(10), 789-799.
Fox, H. S., Bond, B. L., & Parslow, T. G. (1991). Estrogen regulates the IFN-gamma promoter. Journal of immunology (Baltimore, Md.: 1950), 146(12), 4362-4367.
Gadi, N., Wu, S. C., Spihlman, A. P., & Moulton, V. R. (2020). What’s sex got to do with COVID-19? Gender-based differences in the host immune response to coronaviruses. Frontiers in immunology, 11, 562631.
Gebhard, C., Regitz-Zagrosek, V., Neuhauser, H. K., Morgan, R., & Klein, S. L. (2020). Impact of sex and gender on COVID-19 outcomes in Europe. Biology of sex differences, 11, 1-13.
Guan, W. J., Ni, Z. Y., Hu, Y., Liang, W. H., Ou, C. Q., He, J. X., ... & Zhong, N. S. (2020). Clinical characteristics of coronavirus disease 2019 in China. New England journal of medicine, 382(18), 1708-1720.
Henry, B. M., & Lippi, G. (2020). Chronic kidney disease is associated with severe coronavirus disease 2019 (COVID-19) infection. International urology and nephrology, 52, 1193-1194.
Hewagama, A., Patel, D., Yarlagadda, S., Strickland, F. M., & Richardson, B. C. (2009). Stronger inflammatory/cytotoxic T-cell response in women identified by microarray analysis. Genes & Immunity, 10(5), 509-516.
Hirano, T., & Murakami, M. (2020). COVID-19: a new virus, but a familiar receptor and cytokine release syndrome. Immunity, 52(5), 731-733.
Hu, Z. J., Yin, J. M., & Feng, Y. M. (2020). Lower circulating interferon-gamma is a risk factor for lung fibrosis in COVID-19 patients. Frontiers in immunology, 11, 585647.
Jadoo, S. A. A., Alhusseiny, A. H., Yaseen, S. M., Al-Samarrai, M. A. M., Al-Delaimy, A. K., Abed, M. W., & Hassooni, H. R. (2020). Knowledge, attitude, and practice toward COVID-19 among Iraqi people: A web-based cross-sectional study. Journal of Ideas in Health, 3(Special2), 258-265.
Jung, S. Y., Kim, B. G., Kwon, D., Park, J. H., Youn, S. K., Jeon, S., ... & Park, B. J. (2015). An outbreak of joint and cutaneous infections caused by non-tuberculous mycobacteria after corticosteroid injection. International Journal of Infectious Diseases, 36, 62-69.
Klein, S. L., & Flanagan, K. L. (2016). Sex differences in immune responses. Nature Reviews Immunology, 16(10), 626-638.
Klein, S. L., Jedlicka, A., & Pekosz, A. (2010). The Xs and Y of immune responses to viral vaccines. The Lancet Infectious Diseases, 10(5), 338-349.
Kovats, S., Carreras, E., & Agrawal, H. (2009). Sex steroid receptors in immune cells. In H. Agrawal (Ed.), Sex hormones and immunity to infection (pp. 53-91). Berlin, Heidelberg: Springer Berlin Heidelberg.
Lazar, A. M. (2021). ACE2 enzymatic role in the SARS-CoV-2 activation: A perspective through the evolutionary promiscuity and substrate diversity of enzymes. Journal of Ideas in Health, 4(4), 581-587.
Lee, A. J., & Ashkar, A. A. (2018). The dual nature of type I and type II interferons. Frontiers in Immunology, 9, 403701.
Li, P. J., Jin, T., Luo, D. H., Shen, T., Mai, D. M., Hu, W. H., & Mo, H. Y. (2015). Effect of prolonged radiotherapy treatment time on survival outcomes after intensity-modulated radiation therapy in nasopharyngeal carcinoma. PloS One, 10(10), e0141332.
Liu, W., Tao, Z. W., Wang, L., Yuan, M. L., Liu, K., Zhou, L., ... & Hu, Y. (2020). Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease. Chinese Medical Journal, 133(09), 1032-1038.
Lu, L., Zhang, H., Dauphars, D. J., & He, Y. W. (2021). A potential role of interleukin 10 in COVID-19 pathogenesis. Trends in Immunology, 42(1), 3-5.
Markle, J. G., Frank, D. N., Mortin-Toth, S., Robertson, C. E., Feazel, L. M., Rolle-Kampczyk, U., ... & Danska, J. S. (2013). Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science, 339(6123), 1084-1088.
Melgert, B. N., Oriss, T. B., Qi, Z., Dixon-McCarthy, B., Geerlings, M., Hylkema, M. N., & Ray, A. (2010). Macrophages: regulators of sex differences in asthma?. American journal of respiratory cell and molecular biology, 42(5), 595-603.
Moulton, V. R. (2018). Sex hormones in acquired immunity and autoimmune disease. Frontiers in immunology, 9, 414334.
OpenSAFELY Collaborative, Williamson, E., Walker, A. J., Bhaskaran, K., Bacon, S., Bates, C., ... & Goldacre, B. (2020). OpenSAFELY: factors associated with COVID-19-related hospital death in the linked electronic health records of 17 million adult NHS patients. MedRxiv, 2020-05.
Patel, S. K., Velkoska, E., & Burrell, L. M. (2013). Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in?. Clinical and Experimental Pharmacology and Physiology, 40(8), 551-559.
Peretz, J., Pekosz, A., Lane, A. P., & Klein, S. L. (2016). Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors. American Journal of Physiology-Lung Cellular and Molecular Physiology, 310(5), L415-L425.
Potere, N., Batticciotto, A., Vecchié, A., Porreca, E., Cappelli, A., Abbate, A., ... & Bonaventura, A. (2021). The role of IL-6 and IL-6 blockade in COVID-19. Expert review of clinical immunology, 17(6), 601-618.
Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., ... & Tian, D. S. (2020). Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical infectious diseases, 71(15), 762-768.
Rettew, J. A., Huet-Hudson, Y. M., & Marriott, I. (2008). Testosterone reduces macrophage expression in the mouse of toll-like receptor 4, a trigger for inflammation and innate immunity. Biology of reproduction, 78(3), 432-437.
Rozenberg, S., Vandromme, J., & Martin, C. (2020). Are we equal in adversity? Does Covid-19 affect women and men differently?. Maturitas, 138, 62-68.
Souyris, M., Cenac, C., Azar, P., Daviaud, D., Canivet, A., Grunenwald, S., ... & Guéry, J. C. (2018). TLR7 escapes X chromosome inactivation in immune cells. Science Immunology, 3(19), eaap8855.
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology, 20(6), 363-374.
Thompson, A. E., Anisimowicz, Y., Miedema, B., Hogg, W., Wodchis, W. P., & Aubrey-Bassler, K. (2016). The influence of gender and other patient characteristics on health care-seeking behaviour: a QUALICOPC study. BMC Family Practice, 17, 1-7.
Torcia, M. G., Nencioni, L., Clemente, A. M., Civitelli, L., Celestino, I., Limongi, D., ... & Palamara, A. T. (2012). Sex differences in the response to viral infections: TLR8 and TLR9 ligand stimulation induce higher IL10 production in males. PLoS One, 7(6), e39853.
Visuddho, V., Subagjo, A., Setyoningrum, R. A., & Rosyid, A. N. (2021). Predictive accuracy of blood inflammatory markers on COVID-19 mortality. Journal of Ideas in Health, 4(Special4), 623-629.
vom Steeg, L. G., & Klein, S. L. (2016). SeXX matters in infectious disease pathogenesis. PLoS Pathogens, 12(2), e1005374.
Wan, S., Xiang, Y. I., Fang, W., Zheng, Y., Li, B., Hu, Y., ... & Yang, R. (2020). Clinical features and treatment of COVID-19 patients in northeast Chongqing. Journal of Medical Virology, 92(7), 797-806.
Weinstein, Y. A. C. O. B., Ran, S. O. F. I. A., & Segal, S. H. R. A. G. A. (1984). Sex-associated differences in the regulation of immune responses controlled by the MHC of the mouse. Journal of Immunology (Baltimore, Md.: 1950), 132(2), 656-661.
Wenham, C., Smith, J., & Morgan, R. (2020). COVID-19: the gendered impacts of the outbreak. The Lancet, 395(10227), 846-848.
Yuan, X., Huang, W., Ye, B., Chen, C., Huang, R., Wu, F., ... & Hu, J. (2020). Changes of hematological and immunological parameters in COVID-19 patients. International Journal of Hematology, 112, 553-559.
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., ... & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet, 395(10229), 1054-1062.
Zuin, M., Rigatelli, G., Zuliani, G., Rigatelli, A., Mazza, A., & Roncon, L. (2020). Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis. The Journal of Infection, 81(1), e84.
View Dimensions
View Altmetric
Save
Citation
View
Share