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Combined effect of anti‐high‐mobility group box‐1 monoclonal antibody and peramivir against influenza A virus‐induced pneumonia in mice
Author(s) -
Hatayama Kazuki,
Nosaka Nobuyuki,
Yamada Mutsuko,
Yashiro Masato,
Fujii Yosuke,
Tsukahara Hirokazu,
Liu Keyue,
Nishibori Masahiro,
Matsukawa Akihiro,
Morishima Tsuneo
Publication year - 2019
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.25330
Subject(s) - hmgb1 , monoclonal antibody , neuraminidase inhibitor , medicine , influenza a virus , virus , pneumonia , virology , immunology , viral pneumonia , oseltamivir , lung , neuraminidase , antibody , inflammation , pathology , covid-19 , infectious disease (medical specialty) , disease
Human pandemic H1N1 2009 influenza virus causes significant morbidity and mortality with severe acute lung injury due to the excessive inflammatory reaction, even with neuraminidase inhibitor use. The anti‐inflammatory effect of anti‐high‐mobility group box‐1 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti‐HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine‐week‐old male C57BL/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post‐infection (dpi). The anti‐HMGB1 mAb or a control mAb was administered at 2, 3, and 4 dpi. Survival rates were assessed, and lung lavage and pathological analyses were conducted at 5 and 7 dpi. The combination of peramivir with the anti‐HMGB1 mAb significantly improved survival rate whereas the anti‐HMGB1 mAb alone did not affect virus proliferation in the lungs. This combination therapy also significantly ameliorated histopathological changes, neutrophil infiltration, and macrophage aggregation by inhibiting HMGB1, inflammatory cytokines, and oxidative stress. Fluorescence immunostaining showed that the anti‐HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti‐HMGB1 with conventional anti‐influenza therapy might be useful against severe influenza virus infection.