Peripheral Blood Mononuclear Cell Cytokine mRNA Profiles in Acute Respiratory Infection Patients

Introduction: Respiratory infections, collectively, are one of the World's most common and serious illness groups. As recent observations have shown, the most severe courses of acute respiratory infection, often leading to death, are due to uncontrolled cytokine production (hypercytokinemia). Methods: The study involved 364 patients with respiratory illness being treated in clinics in St. Petersburg (Russia) in 2018–2019 and 30 healthy controls. Cytokine analysis was carried out in the acute phase of illness (2–3 days from onset of initial symptoms) and in the stage of recovery (days 9–10). The research presented is devoted to the assessment of mRNA expression of specific cytokines (interleukin [IL]-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α [TNF-α], and interferon-λ) and MxA in whole blood leukocytes, by means of real-time polymerase chain reaction. Results: In 70% of patients, bacterial or viral pathogens were identified, with influenza viral infections (types A and B) prevailing. Significant increases in the expression of IL-18, TNF, and IL-10 were observed, relative to controls, only with influenza viral infections. We have shown a difference in IL-6 mRNA expression in patients with bacterial or viral pathogens. No statistically significant difference was found in white blood cells IL-4 expression levels between patients and healthy controls. Conclusion: Investigation of the nuances of systemic cytokine production, in response to specific viral and bacterial pathogens, makes it possible to assess the risks of developing hypercytokinemia during respiratory infection with agents circulating in the human population and to predict the pathogenicity and virulence of circulating threats.

[1]  A. Vasin,et al.  Epidemiological and clinical features of acute respiratory infections occurring in St. Petersburg during the 2017–2018 and 2018–2019 epidemic seasons , 2020, Journal Infectology.

[2]  Zhenghao Xu,et al.  Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies , 2020, Frontiers in Immunology.

[3]  Chongge You,et al.  Cytokine storm induced by SARS-CoV-2 , 2020, Clinica Chimica Acta.

[4]  J. Teijaro Cytokine storms in infectious diseases , 2017, Seminars in Immunopathology.

[5]  Xi-zhi J. Guo,et al.  New fronts emerge in the influenza cytokine storm , 2017, Seminars in Immunopathology.

[6]  S. Perlman,et al.  Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology , 2017, Seminars in Immunopathology.

[7]  P. Gibson,et al.  The Expression of IL-6, TNF-α, and MCP-1 in Respiratory Viral Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease , 2017, Journal of immunology research.

[8]  V. Martín,et al.  IL-10: A Multifunctional Cytokine in Viral Infections , 2017, Journal of immunology research.

[9]  A. Vasin,et al.  Development of a multiplex quantitative PCR assay for the analysis of human cytokine gene expression in influenza A virus-infected cells. , 2016, Journal of immunological methods.

[10]  T. Michiels,et al.  Interferon-λ in the Context of Viral Infections: Production, Response and Therapeutic Implications , 2014, Journal of Innate Immunity.

[11]  Michael G. Katze,et al.  Into the Eye of the Cytokine Storm , 2012, Microbiology and Molecular Reviews.

[12]  G. Rimmelzwaan,et al.  Immune responses to influenza virus infection. , 2011, Virus research.

[13]  Margarida Saraiva,et al.  The regulation of IL-10 production by immune cells , 2010, Nature Reviews Immunology.

[14]  B. Nelson IL-2, Regulatory T Cells, and Tolerance , 2004, The Journal of Immunology.

[15]  J. Butler Immunoglobulin diversity, B-cell and antibody repertoire development in large farm animals. , 1998, Revue scientifique et technique.

[16]  Y. Yamamoto,et al.  Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia. , 1986, Blood.

[17]  A. Munck,et al.  T cell growth factor receptors. Quantitation, specificity, and biological relevance , 1981, The Journal of experimental medicine.