title: Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice.
abstract: BACKGROUND
  Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice.
  
  
  METHODS
  Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation.
  
  
  RESULTS
  Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment.
  
  
  CONCLUSIONS
  Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. pv702xz5@s.okayama-u.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nosaka
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. yashiro@md.okayama-u.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Yashiro
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. prqv5jku@s.okayama-u.ac.jp.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Yamada
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. fujii-y@cc.okayama-u.ac.jp.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. tsukah-h@cc.okayama-u.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Tsukahara
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. liukeyue@md.okayama-u.ac.jp.
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. mbori@md.okayama-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.affiliation: Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. amatsu@md.okayama-u.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsukawa
authors.affiliation: Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. tmorishima@okayamah.rofuku.go.jp.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Morishima
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004285:Dogs; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors* / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse