Article ; Online: Combined effect of anti-high-mobility group box-1 monoclonal antibody and peramivir against influenza A virus-induced pneumonia in mice.
2018 Volume 91, Issue 3, Page(s) 361–369
Abstract: ... The anti-inflammatory effect of anti-high-mobility group box-1 (HMGB1) monoclonal antibody (mAb) against influenza ... against pneumonia induced by influenza A (H1N1) virus in mice. Nine-week-old male C57BL/6 mice were ... pneumonia has been reported. In this study, we evaluated the combined effect of anti-HMGB1 mAb and peramivir ...
| Abstract | 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. |
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| MeSH term(s) | Animals ; Antibodies, Monoclonal/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclopentanes/therapeutic use ; Cytokines/antagonists & inhibitors ; Drug Therapy, Combination ; Guanidines/therapeutic use ; HMGB1 Protein/immunology ; Inflammation/drug therapy ; Injections, Intramuscular ; Lung/virology ; Male ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration/drug effects ; Orthomyxoviridae Infections/drug therapy ; Orthomyxoviridae Infections/virology ; Pneumonia, Viral/drug therapy | |||||
| Chemical Substances | Antibodies, Monoclonal ; Antiviral Agents ; Cyclopentanes ; Cytokines ; Guanidines ; HMGB1 Protein ; peramivir (QW7Y7ZR15U) | |||||
| Language | English | |||||
| Publishing date | 2018-10-22 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 752392-0 | |||||
| ISSN | 1096-9071 ; 0146-6615 | |||||
| ISSN (online) | 1096-9071 | |||||
| ISSN | 0146-6615 | |||||
| DOI | 10.1002/jmv.25330 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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