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Anti-IFN-γ therapy alleviates acute lung injury induced by severe influenza A (H1N1) pdm09 infection in mice.

Authors
  • Liu, Bo1
  • Bao, LinLin2
  • Wang, Li3
  • Li, Fengdi2
  • Wen, Mingjie4
  • Li, Hui5
  • Deng, Wei2
  • Zhang, Xulong4
  • Cao, Bin6
  • 1 Department of Pulmonary and Critical Care Medicine, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Department of Clinical Microbiology, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Huangong Road, Zibo City, Shandong Province, China; Linzi District People's Hospital Affiliated to Binzhou Medical University, Huangong Road, Zibo City, Shandong Province, China. , (China)
  • 2 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC), Beijing, China; Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious, Beijing, China. , (China)
  • 3 Department of Clinical Microbiology, Linzi District People's Hospital, Huangong Road, Zibo City, Shandong Province, China; Zibo City Key Laboratory of Respiratory Infection and Clinical Microbiology, Huangong Road, Zibo City, Shandong Province, China; Linzi District People's Hospital Affiliated to Binzhou Medical University, Huangong Road, Zibo City, Shandong Province, China. , (China)
  • 4 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. , (China)
  • 5 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center of Respiratory Diseases, Beijing, China; Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. , (China)
  • 6 Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, China; National Clinical Research Center of Respiratory Diseases, Beijing, China; Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Beijing, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
Publication Date
Jun 01, 2021
Volume
54
Issue
3
Pages
396–403
Identifiers
DOI: 10.1016/j.jmii.2019.07.009
PMID: 31780358
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Severe infection with influenza A (H1N1)pdm09 virus is characterized by acute lung injury. The limited efficacy of anti-viral drugs indicates an urgent need for additional therapies. We have previously reported that neutralization of gamma interferon (IFN-γ) could significantly rescue the thymic atrophy induced by severe influenza A (H1N1)pdm09 infection in BALB/c mice. A deeper investigation was conducted into the influence of neutralizing IFN-γ to the BALB/c mice weight, survival rate, and lung injury. The BALB/c mice was infected with severe influenza A (H1N1)pdm09. Monoclonal antibodies against IFN-γ were injected into the abdominal cavities of the mice. After neutralization of IFN-γ occurred in mice infected by severe ∖ influenza A (H1N1)pdm09, observing the influence of neutralizing IFN-γ to the BALB/c mice weight, survival rate, lung injury. Our results here showed that anti-IFN-γ therapy alleviated the acute lung injury in this mouse model. Neutralization of IFN-γ led to a significant reduction in the lung microvascular leak and the cellular infiltrate in the lung tissue, and also improved the outcome in mice mortality. Several pro-inflammatory cytokines, including interleukin (IL)-1α, tumor necrosis factor (TNF)-α and granulocyte-colony stimulating factor (G-CSF) in the bronchoalveolar lavage fluid (BALF), and the chemokines including G-CSF, monocyte chemoattractant protein-1 (MCP-1) in serum samples were found to be significantly reduced after anti-IFN-γ treatment. These results suggested that IFN-γ plays an important role in acute lung injury induced by severe influenza A (H1N1)pdm09 infection, and monoclonal antibodies against IFN-γ could be useful as a potential therapeutic remedy for future influenza pandemics. Copyright © 2019. Published by Elsevier B.V.

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