Bo Liu1, LinLin Bao2, Li Wang3, Fengdi Li2, Mingjie Wen4, Hui Li5, Wei Deng2, Xulong Zhang4, Bin Cao6. 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.
Abstract
BACKGROUND/ PURPOSE: 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. METHODS: 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. RESULT: 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. CONCLUSION: 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.
BACKGROUND/ PURPOSE: 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. METHODS: 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. RESULT: 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. CONCLUSION: 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.
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