Anti-inflammatory interleukins (IL-4 and IL-10) and their relationship with the severity of COVID-19: A systematic review
DOI:
https://doi.org/10.33448/rsd-v14i3.48459Keywords:
COVID-19, Interleukins, Prognosis.Abstract
COVID-19, caused by the coronavirus SARS-CoV-2, was identified in December 2019 in Wuhan, China, following an outbreak of pneumonia. The infection can range from asymptomatic to serious conditions, such as pneumonia and Acute Respiratory Distress Syndrome (ARDS), the main concern. ARDS is classified into levels of severity based on criteria such as time of onset and hypoxemia. SARS-CoV-2 infection causes inflammation and microvascular thrombosis, with emphasis on the "cytokine storm", which worsens the disease, especially in the elderly. Cytokines such as IL-6 and IL-10 are associated with disease severity and their initial levels can help predict prognosis, influencing treatment. The present study aims to carry out a Systematic Literature Review to evaluate the levels of anti-inflammatory cytokines, especially IL-10, in patients with COVID-19 and their relationship with severity, especially in respiratory disorders such as ARDS. The search was carried out in the Pubmed and Lilacs databases, with the inclusion of primary studies and strict eligibility criteria. 197 articles were analyzed, with 13 being considered eligible. The results show that high levels of IL-10 are associated with severe forms of COVID-19, especially elderly patients and patients with comorbidities, who are more susceptible to ARDS. IL-10, in combination with IL-6, can serve as a biomarker to predict disease severity. However, the study has limitations, such as small sample sizes and the lack of comparisons with other inflammatory diseases. Although IL-10 holds promise as an early marker, further studies are needed to confirm its efficacy and determine therapeutic approaches. The combination of cytokines and other clinical findings should be considered in the prognosis of COVID-19.
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Abers, M. S., et al. (2021). An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight. https://doi.org/10.1172/jci.insight.141299
Akbari, H., et al. (2020). The role of cytokine profile and lymphocyte subsets in the severity of coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis. Life Sciences, 258, 1-8. https://doi.org/10.1016/j.lfs.2020.118358
Casarin, S. T. et al. (2020). Tipos de revisão de literatura: considerações das editoras do Journal of Nursing and Health. Journal of Nursing and Health. 10 (5). https://periodicos.ufpel.edu.br/index.php/enfermagem/article/view/19924
Cavalcante, L. T. C. & Oliveira, A. A. S. (2020). Métodos de revisão bibliográfica nos estudos científicos. Psicol. Rev. 26 (1). https://doi.org/10.5752/P.1678-9563.2020v26n1p82-100
Choreño-Parra, J. A., et al. (2021). Clinical and immunological factors that distinguish COVID-19 from pandemic influenza A(H1N1). Frontiers in Immunology, 12, 1-8. https://doi.org/10.3389/fimmu.2021.648321
Dorgham, K., et al. (2021). Distinct cytokine profiles associated with COVID-19 severity and mortality. Journal of Allergy and Clinical Immunology, 147(6), 2098–2107. https://doi.org/10.1016/j.jaci.2021.01.044
Elshazli, R. M., et al. (2020). Diagnostic and prognostic value of hematological and immunological markers in COVID-19 infection: A meta-analysis of 6320 patients. PLoS ONE, 15(8), e0238557. https://doi.org/10.1371/journal.pone.0238557
Han, H., et al. (2020). Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors. Emerging Microbes and Infections, 9(1), 1123–1130. https://doi.org/10.1080/22221751.2020.1781234
Ji, P., et al. (2020). Association of elevated inflammatory markers and severe COVID-19: A meta-analysis. Medicine, 99(47), e23315. https://doi.org/10.1097/MD.0000000000023315
Kim, S. D., & Yeun, Y. R. (2022). Effects of resistance training on C-reactive protein and inflammatory cytokines in elderly adults: A systematic review and meta-analysis of randomized controlled trials. International Journal of Environmental Research and Public Health, 19(5), 1-12. https://doi.org/10.3390/ijerph19052493
Le Bert, N., et al. (2021). Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. Journal of Experimental Medicine, 218(5), 1-9. https://doi.org/10.1084/jem.20210409
Luporini, R. L., et al. (2021). IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19. Elsevier Cytokine, 143, 1-7. https://doi.org/10.1016/j.cyto.2021.155545
Lu, Q., et al. (2021). Changes of serum IL-10, IL-1β, IL-6, MCP-1, TNF-α, IP-10, and IL-4 in COVID-19 patients. International Journal of Clinical Practice, 75(9), 1-9. https://doi.org/10.1111/ijcp.14076
Moher, D., et al. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Medicine, 6(7), 1-6. https://doi.org/10.1371/journal.pmed.1000097
Mosser, D. M., & Zhang, X. (2008). Interleukin-10: New perspectives on an old cytokine. Immunological Reviews, 226, 1-14. https://doi.org/10.1111/j.1600-065X.2008.00706.x
Notz, Q., et al. (2020). Pro- and anti-inflammatory responses in severe COVID-19-induced acute respiratory distress syndrome: An observational pilot study. Frontiers in Immunology, 11, 1-8. https://doi.org/10.3389/fimmu.2020.591280
Orraine, L., Are, B. W., & Atthay, A. M. (2000). The acute respiratory distress syndrome. The New England Journal of Medicine, 342(18), 1334-1348. https://doi.org/10.1056/NEJM200005043421804
P Amato Relator, M. B., et al. (2007). Lesão pulmonar aguda (LPA)/ Síndrome do desconforto respiratório agudo (SDRA): Consenso brasileiro de ventilação mecânica. Jornal Brasileiro de Pneumologia, 3, 119-127.
Pereira A. S. et al. (2018). Metodologia da pesquisa científica. [free e-book]. Editora UAB/NTE/UFSM.
Ranieri, V. M., et al. (2012). Acute respiratory distress syndrome: The Berlin definition. JAMA, 307(23), 2526–2533. https://doi.org/10.1001/jama.2012.5669
Rother, E. T. (2007). Revisão sistemática x revisão narrativa. Acta Paul. Enferm. 20 (2). https://doi.org/10.1590/S0103-21002007000200001.
Valizadeh, H., et al. (2020). Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients. International Immunopharmacology, 89, 1-8. https://doi.org/10.1016/j.intimp.2020.107071
Ye, Q., Wang, B., & Mao, J. (2020). The pathogenesis and treatment of the 'cytokine storm' in COVID-19. Journal of Infection, 80(6), 607-613. https://doi.org/10.1016/j.jinf.2020.03.016
Zhao, Y., et al. (2020). Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease. JCI Insight, 5(13), 1-8. https://doi.org/10.1172/jci.insight.141299
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Copyright (c) 2025 Gabriel Cerqueira Santos; Carolina Moura Almeida; Eduardo Chaves Ferreira Coelho; Ricardo Silva Freire; Alyssa Alves Fernandes Silva; Letícia Romeira Belchior; Irmtraut Araci Hoffmann Pfrimer
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