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

tetano

Editor, Senior Moderator
J Microbiol Immunol Infect. 2019 Nov 12. pii: S1684-1182(18)30438-9. doi: 10.1016/j.jmii.2019.07.009. [Epub ahead of print] [h=1]Anti-IFN-γ therapy alleviates acute lung injury induced by severe influenza A (H1N1) pdm09 infection in mice.[/h]
Liu B[SUP]1[/SUP], Bao L[SUP]2[/SUP], Wang L[SUP]3[/SUP], Li F[SUP]2[/SUP], Wen M[SUP]4[/SUP], Li H[SUP]5[/SUP], Deng W[SUP]2[/SUP], Zhang X[SUP]4[/SUP], Cao B[SUP]6[/SUP].
[h=3]Author information[/h] 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. 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. 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. 4 Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, 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. 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: caobin_ben@163.com.

[h=3]Abstract[/h] [h=4]BACKGROUND/PURPOSE:[/h] 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.
[h=4]METHODS:[/h] 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.
[h=4]RESULT:[/h] 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.
[h=4]CONCLUSION:[/h] 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.


[h=4]KEYWORDS:[/h] H1N1; IFN-γ; Lung injury

PMID: 31780358 DOI: 10.1016/j.jmii.2019.07.009
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