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The anti\u2010inflammatory effect of anti\u2010high\u2010mobility group box\u20101 (HMGB1) monoclonal antibody (mAb) against influenza pneumonia has been reported. In this study, we evaluated the combined effect of anti\u2010HMGB1 mAb and peramivir against pneumonia induced by influenza A (H1N1) virus in mice. Nine\u2010week\u2010old male C57BL\/6 mice were inoculated with H1N1 and treated with intramuscularly administered peramivir at 2 and 3 days post\u2010infection (dpi). The anti\u2010HMGB1 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\u2010HMGB1 mAb significantly improved survival rate whereas the anti\u2010HMGB1 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\u2010HMGB1 mAb inhibited HMGB1 translocation from type I alveolar epithelial cells. In summary, combining anti\u2010HMGB1 with conventional anti\u2010influenza therapy might be useful against severe influenza virus infection.<\/jats:p>","DOI":"10.1002\/jmv.25330","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T15:44:02Z","timestamp":1538754242000},"page":"361-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Combined effect of anti\u2010high\u2010mobility group box\u20101 monoclonal antibody and peramivir against influenza A virus\u2010induced pneumonia in mice"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1390-7715","authenticated-orcid":false,"given":"Kazuki","family":"Hatayama","sequence":"first","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-0701","authenticated-orcid":false,"given":"Nobuyuki","family":"Nosaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsuko","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Yashiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yosuke","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Tsukahara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nishibori","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Matsukawa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuneo","family":"Morishima","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Okayama Japan"},{"name":"Department of Pediatrics Aichi Medical University  Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,10,22]]},"reference":[{"key":"e_1_2_9_1_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1496"},{"key":"e_1_2_9_1_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1536"},{"key":"e_1_2_9_1_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908481"},{"key":"e_1_2_9_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.icb.7100026"},{"key":"e_1_2_9_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08260"},{"key":"e_1_2_9_1_7_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100115"},{"key":"e_1_2_9_1_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44947"},{"key":"e_1_2_9_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2011.07.016"},{"key":"e_1_2_9_1_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5425.248"},{"key":"e_1_2_9_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2014.05.001"},{"key":"e_1_2_9_1_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0983-9"},{"key":"e_1_2_9_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.25076"},{"key":"e_1_2_9_1_14_1","unstructured":"CDC. 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