Skip to main content
Top
Published in: BMC Infectious Diseases 1/2022

Open Access 01-12-2022 | Filgrastim | Research

Interleukin-6 and granulocyte colony-stimulating factor as predictors of the prognosis of influenza-associated pneumonia

Authors: Jiaying Zhang, Jingxia Wang, Yiwen Gong, Yudan Gu, Qiangqiang Xiang, Ling-Ling Tang

Published in: BMC Infectious Diseases | Issue 1/2022

Login to get access

Abstract

Background

Pneumonia is a common complication of influenza and closely related to mortality in influenza patients. The present study examines cytokines as predictors of the prognosis of influenza-associated pneumonia.

Methods

This study included 101 inpatients with influenza (64 pneumonia and 37 non-pneumonia patients). 48 cytokines were detected in the serum samples of the patients and the clinical characteristics were analyzed. The correlation between them was analyzed to identify predictive biomarkers for the prognosis of influenza-associated pneumonia.

Results

Seventeen patients had poor prognosis and developed pneumonia. Among patients with influenza-associated pneumonia, the levels of 8 cytokines were significantly higher in those who had a poor prognosis: interleukin-6 (IL-6), interferon-γ (IFN-γ), granulocyte colony-stimulating factor (G-CSF), monocyte colony-stimulating factor (M-CSF), monocyte chemoattractant protein-1 (MCP-1), monocyte chemoattractant protein-3, Interleukin-2 receptor subunit alpha and Hepatocyte growth factor. Correlation analysis showed that the IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had positive correlations with the severity of pneumonia. IL-6 and G-CSF showed a strong and positive correlation with poor prognosis in influenza-associated pneumonia patients. The combined effect of the two cytokines resulted in the largest area (0.926) under the receiver-operating characteristic curve.

Conclusion

The results indicate that the probability of poor prognosis in influenza patients with pneumonia is significantly increased. IL-6, G-CSF, M-CSF, IFN-γ, and MCP-1 levels had a positive correlation with the severity of pneumonia. Importantly, IL-6 and G-CSF were identified as significant predictors of the severity of influenza-associated pneumonia.
Appendix
Available only for authorised users
Literature
1.
go back to reference Paules C, Subbarao K. Influenza. Lancet (London, England). 2017;390(10095):697–708.CrossRef Paules C, Subbarao K. Influenza. Lancet (London, England). 2017;390(10095):697–708.CrossRef
3.
go back to reference Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ (Clinical research ed). 2013;347:f5061.PubMedCentral Mertz D, Kim TH, Johnstone J, et al. Populations at risk for severe or complicated influenza illness: systematic review and meta-analysis. BMJ (Clinical research ed). 2013;347:f5061.PubMedCentral
4.
go back to reference Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16–32.CrossRef Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, Katze MG. Into the eye of the cytokine storm. Microbiol Mol Biol Rev. 2012;76(1):16–32.CrossRef
5.
go back to reference Guo XJ, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 2017;39(5):541–50.CrossRef Guo XJ, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol. 2017;39(5):541–50.CrossRef
6.
go back to reference Paats MS, Bergen IM, Hanselaar WE, et al. Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia. Eur Respir J. 2013;41(6):1378–85.CrossRef Paats MS, Bergen IM, Hanselaar WE, et al. Local and systemic cytokine profiles in nonsevere and severe community-acquired pneumonia. Eur Respir J. 2013;41(6):1378–85.CrossRef
7.
go back to reference Brown PM, Schneeberger DL, Piedimonte G. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity. Paediatr Respir Rev. 2015;16(4):232–40.PubMedPubMedCentral Brown PM, Schneeberger DL, Piedimonte G. Biomarkers of respiratory syncytial virus (RSV) infection: specific neutrophil and cytokine levels provide increased accuracy in predicting disease severity. Paediatr Respir Rev. 2015;16(4):232–40.PubMedPubMedCentral
8.
go back to reference Bian JR, Nie W, Zang YS, Fang Z, Xiu QY, Xu XX. Clinical aspects and cytokine response in adults with seasonal influenza infection. Int J Clin Exp Med. 2014;7(12):5593–602.PubMedPubMedCentral Bian JR, Nie W, Zang YS, Fang Z, Xiu QY, Xu XX. Clinical aspects and cytokine response in adults with seasonal influenza infection. Int J Clin Exp Med. 2014;7(12):5593–602.PubMedPubMedCentral
9.
go back to reference Teijaro JR. Cytokine storms in infectious diseases. Semin Immunopathol. 2017;39(5):501–3.CrossRef Teijaro JR. Cytokine storms in infectious diseases. Semin Immunopathol. 2017;39(5):501–3.CrossRef
10.
go back to reference Wong SS, Oshansky CM, Guo XJ, et al. Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study. J Infect Dis. 2018;217(2):245–56.CrossRef Wong SS, Oshansky CM, Guo XJ, et al. Severe influenza is characterized by prolonged immune activation: results from the SHIVERS cohort study. J Infect Dis. 2018;217(2):245–56.CrossRef
11.
go back to reference Oldstone MB, Rosen H. Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule. Curr Top Microbiol Immunol. 2014;378:129–47.PubMedPubMedCentral Oldstone MB, Rosen H. Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule. Curr Top Microbiol Immunol. 2014;378:129–47.PubMedPubMedCentral
12.
go back to reference Ryabkova VA, Churilov LP, Shoenfeld Y. Influenza infection, SARS, MERS and COVID-19: Cytokine storm—the common denominator and the lessons to be learned. Clin Immunol (Orlando, Fla). 2021;223:108652.CrossRef Ryabkova VA, Churilov LP, Shoenfeld Y. Influenza infection, SARS, MERS and COVID-19: Cytokine storm—the common denominator and the lessons to be learned. Clin Immunol (Orlando, Fla). 2021;223:108652.CrossRef
13.
go back to reference Oliveira EC, Marik PE, Colice G. Influenza pneumonia: a descriptive study. Chest. 2001;119(6):1717–23.CrossRef Oliveira EC, Marik PE, Colice G. Influenza pneumonia: a descriptive study. Chest. 2001;119(6):1717–23.CrossRef
14.
go back to reference Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F. Role of monocytes/macrophages in Covid-19 pathogenesis: implications for therapy. Infect Drug Resist. 2020;13:2485–93.CrossRef Gómez-Rial J, Rivero-Calle I, Salas A, Martinón-Torres F. Role of monocytes/macrophages in Covid-19 pathogenesis: implications for therapy. Infect Drug Resist. 2020;13:2485–93.CrossRef
15.
go back to reference Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspect Biol. 2014;6(10):a016295.CrossRef Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspect Biol. 2014;6(10):a016295.CrossRef
16.
go back to reference Blanton L, Mustaquim D, Alabi N, et al. Update: influenza activity—United States, October 2, 2016-February 4, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(6):159–66.CrossRef Blanton L, Mustaquim D, Alabi N, et al. Update: influenza activity—United States, October 2, 2016-February 4, 2017. MMWR Morb Mortal Wkly Rep. 2017;66(6):159–66.CrossRef
17.
go back to reference Del Giudice M, Gangestad SW. Rethinking IL-6 and CRP: why they are more than inflammatory biomarkers, and why it matters. Brain Behav Immun. 2018;70:61–75.CrossRef Del Giudice M, Gangestad SW. Rethinking IL-6 and CRP: why they are more than inflammatory biomarkers, and why it matters. Brain Behav Immun. 2018;70:61–75.CrossRef
18.
go back to reference Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448–57.CrossRef Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448–57.CrossRef
19.
go back to reference Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J. 2015;45(5):1463–78.CrossRef Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J. 2015;45(5):1463–78.CrossRef
20.
go back to reference Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009;29(6):313–26.CrossRef Deshmane SL, Kremlev S, Amini S, Sawaya BE. Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interferon Cytokine Res. 2009;29(6):313–26.CrossRef
21.
go back to reference Wang J, Nikrad MP, Travanty EA, et al. Innate immune response of human alveolar macrophages during influenza A infection. PloS One. 2012;7(3):e29879.CrossRef Wang J, Nikrad MP, Travanty EA, et al. Innate immune response of human alveolar macrophages during influenza A infection. PloS One. 2012;7(3):e29879.CrossRef
22.
go back to reference Liu Y, Chen H, Sun Y, Chen F. Antiviral role of Toll-like receptors and cytokines against the new 2009 H1N1 virus infection. Mol Biol Rep. 2012;39(2):1163–72.CrossRef Liu Y, Chen H, Sun Y, Chen F. Antiviral role of Toll-like receptors and cytokines against the new 2009 H1N1 virus infection. Mol Biol Rep. 2012;39(2):1163–72.CrossRef
23.
go back to reference Shen Z, Chen Z, Li X, et al. Host immunological response and factors associated with clinical outcome in patients with the novel influenza A H7N9 infection. Clin Microbiol Infect. 2014;20(8):O493-500.CrossRef Shen Z, Chen Z, Li X, et al. Host immunological response and factors associated with clinical outcome in patients with the novel influenza A H7N9 infection. Clin Microbiol Infect. 2014;20(8):O493-500.CrossRef
24.
go back to reference Narasaraju T, Yang E, Samy RP, et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011;179(1):199–210.CrossRef Narasaraju T, Yang E, Samy RP, et al. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol. 2011;179(1):199–210.CrossRef
25.
go back to reference Ashar HK, Mueller NC, Rudd JM, et al. The role of extracellular histones in influenza virus pathogenesis. Am J Pathol. 2018;188(1):135–48.CrossRef Ashar HK, Mueller NC, Rudd JM, et al. The role of extracellular histones in influenza virus pathogenesis. Am J Pathol. 2018;188(1):135–48.CrossRef
26.
go back to reference Block H, Zarbock A. A fragile balance: does neutrophil extracellular trap formation drive pulmonary disease progression? Cells. 2021;10(8):1932.CrossRef Block H, Zarbock A. A fragile balance: does neutrophil extracellular trap formation drive pulmonary disease progression? Cells. 2021;10(8):1932.CrossRef
27.
go back to reference Lazzaretto B, Fadeel B. Intra- and extracellular degradation of neutrophil extracellular traps by macrophages and dendritic cells. J Immunol (Baltimore, Md: 1950). 2019;203(8):2276–90.CrossRef Lazzaretto B, Fadeel B. Intra- and extracellular degradation of neutrophil extracellular traps by macrophages and dendritic cells. J Immunol (Baltimore, Md: 1950). 2019;203(8):2276–90.CrossRef
28.
go back to reference Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in neutropenia. J Immunol (Baltimore, Md: 1950). 2015;195(4):1341–9.CrossRef Mehta HM, Malandra M, Corey SJ. G-CSF and GM-CSF in neutropenia. J Immunol (Baltimore, Md: 1950). 2015;195(4):1341–9.CrossRef
29.
go back to reference Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018;17(6):395–412.CrossRef Garbers C, Heink S, Korn T, Rose-John S. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018;17(6):395–412.CrossRef
30.
go back to reference Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother. 2017;13(9):1972–88.CrossRef Sheppard M, Laskou F, Stapleton PP, Hadavi S, Dasgupta B. Tocilizumab (Actemra). Hum Vaccin Immunother. 2017;13(9):1972–88.CrossRef
31.
go back to reference Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (London, England: 1979). 2012;122(4):143–59.CrossRef Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (London, England: 1979). 2012;122(4):143–59.CrossRef
32.
go back to reference Zongfei J, Rongyi C, Xiaomeng C, et al. In vitro IL-6/IL-6R trans-signaling in fibroblasts releases cytokines that may be linked to the pathogenesis of IgG4-related disease. Front Immunol. 2020;11:1272.CrossRef Zongfei J, Rongyi C, Xiaomeng C, et al. In vitro IL-6/IL-6R trans-signaling in fibroblasts releases cytokines that may be linked to the pathogenesis of IgG4-related disease. Front Immunol. 2020;11:1272.CrossRef
33.
go back to reference Rello J, Waterer GW, Bourdiol A, Roquilly A. COVID-19, steroids and other immunomodulators: the jigsaw is not complete. Anaesth Crit Care Pain Med. 2020;39(6):699–701.CrossRef Rello J, Waterer GW, Bourdiol A, Roquilly A. COVID-19, steroids and other immunomodulators: the jigsaw is not complete. Anaesth Crit Care Pain Med. 2020;39(6):699–701.CrossRef
34.
go back to reference Wang H, Aloe C, Wilson N, Bozinovski S. G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance. Sci Rep. 2019;9(1):17732.CrossRef Wang H, Aloe C, Wilson N, Bozinovski S. G-CSFR antagonism reduces neutrophilic inflammation during pneumococcal and influenza respiratory infections without compromising clearance. Sci Rep. 2019;9(1):17732.CrossRef
35.
go back to reference Scalzo-Inguanti K, Monaghan K, Edwards K, et al. A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates. J Leukoc Biol. 2017;102(2):537–49.CrossRef Scalzo-Inguanti K, Monaghan K, Edwards K, et al. A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates. J Leukoc Biol. 2017;102(2):537–49.CrossRef
Metadata
Title
Interleukin-6 and granulocyte colony-stimulating factor as predictors of the prognosis of influenza-associated pneumonia
Authors
Jiaying Zhang
Jingxia Wang
Yiwen Gong
Yudan Gu
Qiangqiang Xiang
Ling-Ling Tang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2022
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07321-6

Other articles of this Issue 1/2022

BMC Infectious Diseases 1/2022 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.