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Volume 12, Issue 2 (Vol.12 No.2 Jul 2023)
rbmb.net 2023, 12(2): 284-293 |
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Rostami-Far Z, Rahmani K, Mansouri K, Khadem Erfan M B, Shaveisi-Zadeh F, Nikkhoo B. Genetic Regulation of Interleukin-6 and Interleukin-10 in COVID-19 Infection. rbmb.net 2023; 12 (2) :284-293
URL: http://rbmb.net/article-1-1098-en.html
URL: http://rbmb.net/article-1-1098-en.html
Zahra Rostami-Far 
, Khaled Rahmani , Kamran Mansouri , Mohammad Bagher Khadem Erfan , Farhad Shaveisi-Zadeh , Bahram Nikkhoo *
, Khaled Rahmani , Kamran Mansouri , Mohammad Bagher Khadem Erfan , Farhad Shaveisi-Zadeh , Bahram Nikkhoo *
Department of Pathology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Abstract: (974 Views)
Background: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood.
Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively.
Results: The male ratio and mean age of critically ill patients’ group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls.
Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.
Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively.
Results: The male ratio and mean age of critically ill patients’ group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls.
Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.
Keywords: COVID-19, Gene Expression, Interleukin-6 (IL-6), Interleukin-10 (IL-10), SARS-COV-2, Promoter Methylation.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2022/11/18 | Accepted: 2023/01/22 | Published: 2023/12/20
Received: 2022/11/18 | Accepted: 2023/01/22 | Published: 2023/12/20
References
1. Zhang C, Wu Z, Li J-W, Zhao H, Wang G-Q. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020;55(5):105954. [DOI:10.1016/j.ijantimicag.2020.105954] [PMID] []
2. Shaveisi-Zadeh F, Nikkho B, Khadem Erfan MB, Amiri A, Azizi A, Mansouri N, et al. Changes in liver enzymes and association with prognosis in patients with COVID-19: a retrospective case-control study. J Int Med Res. 2022;50(7):03000605221110067. [DOI:10.1177/03000605221110067] [PMID] []
3. Maradi R, Joshi V, Balamurugan V, Susan Thomas D, Goud M. Importance of Microminerals for Maintaining Antioxidant Function After COVID-19-induced Oxidative Stress. Rep Biochem Mol Biol. 2022;11(3):479-486. [DOI:10.52547/rbmb.11.3.479] [PMID] []
4. Han H, Ma Q, Li C, Liu R, Zhao L, Wang W, et al. Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerg Microbes Infect. 2020;9(1):1123-30. [DOI:10.1080/22221751.2020.1770129] [PMID] []
5. Mostafa-Hedeab G. ACE2 as Drug Target of COVID- 19 Virus Treatment, Simplified Updated Review. Rep Biochem Mol Biol. 2020;9(1):97-105. [DOI:10.29252/rbmb.9.1.97] [PMID] []
6. Xia C, Liu Y, Chen Z, Zheng M. Involvement of Interleukin 6 in Hepatitis B Viral Infection. Cell Physiol Biochem. 2015;37(2):677-86. [DOI:10.1159/000430386] [PMID]
7. Rizvi S, Rizvi SMS, Raza ST, Abbas M, Fatima K, Zaidi ZH, Mahdi F. Implication of single nucleotide polymorphisms in Interleukin-10 gene (rs1800896 and rs1800872) with severity of COVID-19. Egypt J Med Hum Genet. 2022;23(1):145. [DOI:10.1186/s43042-022-00344-3] [PMID] []
8. Santos JGO, Migueis DP, Amaral JBD, Bachi ALL, Boggi AC, Thamboo A, et al. Impact of SARS-CoV-2 on saliva: TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM. J Oral Biosci. 2022;64(1):108-113. [DOI:10.1016/j.job.2022.01.007] [PMID] []
9. Saksena N, Bonam SR, Miranda-Saksena M. Epigenetic Lens to Visualize the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Infection in COVID-19 Pandemic. Front Genet. 2021;12:581726. [DOI:10.3389/fgene.2021.581726] [PMID] []
10. Qin W, Scicluna BP, van der Poll T. The Role of Host Cell DNA Methylation in the Immune Response to Bacterial Infection. Front Immunol. 2021;12:696280. [DOI:10.3389/fimmu.2021.696280] [PMID] []
11. Anderson D, Neri JICF, Souza CRM, Valverde JG, De Araújo JMG, Nascimento MDSB, Branco RCC, Arrais NMR, Lassmann T, Blackwell JM, Jeronimo SMB. Zika Virus Changes Methylation of Genes Involved in Immune Response and Neural Development in Brazilian Babies Born With Congenital Microcephaly. J Infect Dis. 2021;223(3):435-440. [DOI:10.1093/infdis/jiaa383] [PMID]
12. World Health Organization. Geneva: World Health Organization; 2020. Global surveillance for COVID-19 caused by human infection with COVID-19 virus: interim guidance. 2020.
13. Goldenberg D, Benoit NE, Begum S, Westra WH, Cohen Y, Koch WM, et al. Epstein-Barr virus in head and neck cancer assessed by quantitative polymerase chain reaction. Laryngoscope. 2004;114(6):1027-31. [DOI:10.1097/00005537-200406000-00013] [PMID]
14. Omar WFNW, Abdullah A, Talib NA, Shah ASM, Rahman JA. Leucocytic DNA Methylation of Interleukin-6 Promoter Reduction in Pre-Hypertensive Young Adults. Malays J Med Sci. 2019;26(6):46-54. [DOI:10.21315/mjms2019.26.6.5] [PMID] []
15. Tang J, P Tang J, Pan R, Xu L, Ma Q, Ying X, et al. IL10 hypomethylation is associated with the risk of gastric cancer. Oncol Lett. 2021;21(4):241. [DOI:10.3892/ol.2021.12502] [PMID] []
16. Cen C, McGinn J, Aziz M, Yang WL, Cagliani J, Nicastro JM, et al. Deficiency in cold-inducible RNA-binding protein attenuates acute respiratory distress syndrome induced by intestinal ischemia-reperfusion. Surgery. 2017;162(4):917-927. [DOI:10.1016/j.surg.2017.06.004] [PMID]
17. Zhao M, Tang J, Gao F, Wu X, Liang Y, et al. Hypomethylation of IL10 and IL13 promoters in CD4+ T cells of patients with systemic lupus erythematosus. J Biomed Biotechnol. 2010;2010:931018. [DOI:10.1155/2010/931018] [PMID] []
18. Ghotbi N. The COVID-19 Pandemic Response and Its Impact on Post-Corona Health Emergency and Disaster Risk Management in Iran. Sustainability. 2022;14(22):1-13. [DOI:10.3390/su142214858]
19. Bwire GM. Coronavirus: Why Men are More Vulnerable to Covid-19 Than Women? SN Compr Clin Med. 2020;2(7):874-876. [DOI:10.1007/s42399-020-00341-w] [PMID] []
20. Lorente-Sorolla C, Garcia-Gomez A, Català-Moll F, Toledano V, Ciudad L, Avendaño-Ortiz J, et al. Inflammatory cytokines and organ dysfunction associate with the aberrant DNA methylome of monocytes in sepsis. Genome Med. 2019;11(1):66. [DOI:10.1186/s13073-019-0674-2] [PMID] []
21. Hur K, Niwa T, Toyoda T, Tsukamoto T, Tatematsu M, Yang HK, Ushijima T. Insufficient role of cell proliferation in aberrant DNA methylation induction and involvement of specific types of inflammation. Carcinogenesis. 2011;32(1):35-41. [DOI:10.1093/carcin/bgq219] [PMID]
22. Binnie A, Walsh CJ, Hu P, Dwivedi DJ, Fox-Robichaud A, Liaw PC, et al. Epigenetic Profiling in Severe Sepsis (EPSIS) Study of the Canadian Critical Care Translational Biology Group (CCCTBG). Epigenetic Profiling in Severe Sepsis: A Pilot Study of DNA Methylation Profiles in Critical Illness. Crit Care Med. 2020;48(2):142-150. [DOI:10.1097/CCM.0000000000004097] [PMID]
23. Cizmeci D, Dempster EL, Champion OL, Wagley S, Akman OE, Prior JL, et al. Mapping epigenetic changes to the host cell genome induced by Burkholderia pseudomallei reveals pathogen-specific and pathogen-generic signatures of infection. Sci Rep. 2016;6:30861. [DOI:10.1038/srep30861] [PMID] []
24. Sinclair SH, Yegnasubramanian S, Dumler JS. Global DNA methylation changes and differential gene expression in Anaplasma phagocytophilum-infected human neutrophils. Clin Epigenetics. 2015;7(1):77. [DOI:10.1186/s13148-015-0105-1] [PMID] []
25. Wang S, Young RS, Sun NN, Witten ML. In vitro cytokine release from rat type II pneumocytes and alveolar macrophages following exposure to JP-8 jet fuel in co-culture. Toxicology. 2002;173(3):211-9. [DOI:10.1016/S0300-483X(02)00037-9] [PMID]
26. Castellheim A, Brekke OL, Espevik T, Harboe M, Mollnes TE. Innate immune responses to danger signals in systemic inflammatory response syndrome and sepsis. Scand J Immunol. 2009;69(6):479-91. [DOI:10.1111/j.1365-3083.2009.02255.x] [PMID]
27. Luo M, Liu J, Jiang W, Yue S, Liu H, Wei S. IL-6 and CD8+ T cell counts combined are an early predictor of in-hospital mortality of patients with COVID-19. JCI Insight. 2020;5(13):e139024. [DOI:10.1172/jci.insight.139024] [PMID] []
28. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C, Melguizo-Rodríguez L. SARS-CoV-2 infection: The role of cytokines in COVID-19 disease. Cytokine Growth Factor Rev. 2020;54:62-75. [DOI:10.1016/j.cytogfr.2020.06.001] [PMID] []
29. Wu W, Dietze KK, Gibbert K, Lang KS, Trilling M, Yan H, et al. TLR ligand induced IL-6 counter-regulates the anti-viral CD8(+) T cell response during an acute retrovirus infection. Sci Rep. 2015;5:10501. [DOI:10.1038/srep10501] [PMID] []
30. Filisetti D, Candolfi E. Immune response to Toxoplasma gondii. Ann Ist Super Sanita. 2004;40(1):71-80.
31. Smith LK, Boukhaled GM, Condotta SA, Mazouz S, Guthmiller JJ, Vijay R, et al. Interleukin-10 Directly Inhibits CD8+ T Cell Function by Enhancing N-Glycan Branching to Decrease Antigen Sensitivity. Immunity. 2018;48(2):299-312.e5. [DOI:10.1016/j.immuni.2018.01.006] [PMID] []
32. Yao C, Bora SA, Parimon T, Zaman T, Friedman OA, Palatinus JA, et al. Cell-Type-Specific Immune Dysregulation in Severely Ill COVID-19 Patients. Cell Rep. 2021;34(1):108590. [DOI:10.1016/j.celrep.2020.108590] [PMID] []
33. Hansen CB, Jarlhelt I, Pérez-Alós L, Hummelshøj Landsy L, Loftager M, Rosbjerg A, et al. SARS-CoV-2 Antibody Responses Are Correlated to Disease Severity in COVID-19 Convalescent Individuals. J Immunol. 2021;206(1):109-117. [DOI:10.4049/jimmunol.2000898] [PMID]
34. Yan X, Chen G, Jin Z, Zhang Z, Zhang B, He J, et al. Anti-SARS-CoV-2 IgG levels in relation to disease severity of COVID-19. J Med Virol. 2022;94(1):380-383. [DOI:10.1002/jmv.27274] [PMID] []
35. Phipps WS, SoRelle JA, Li QZ, Mahimainathan L, Araj E, Markantonis J, et al. SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity. Am J Clin Pathol. 2020;154(4):459-465. [DOI:10.1093/ajcp/aqaa123] [PMID] []
36. Steiner S, Schwarz T, Corman VM, Gebert L, Kleinschmidt MC, Wald A, et al. SARS-CoV-2 T Cell Response in Severe and Fatal COVID-19 in Primary Antibody Deficiency Patients Without Specific Humoral Immunity. Front Immunol. 2022;13:840126. [DOI:10.3389/fimmu.2022.840126] [PMID] []
37. Sánchez-Zuno GA, Matuz-Flores MG, González-Estevez G, Nicoletti F, Turrubiates-Hernández FJ, Mangano K, Muñoz-Valle JF. A review: Antibody-dependent enhancement in COVID-19: The not so friendly side of antibodies. Int J Immunopathol Pharmacol. 2021;35:20587384211050199. [DOI:10.1177/20587384211050199] [PMID] []
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