title: Anti-high-mobility group box chromosomal protein 1 antibodies improve survival of rats with sepsis.
abstract: BACKGROUND
  High-mobility group box chromosomal protein 1 (HMGB1) has recently been shown to be an important late mediator of endotoxin shock, intraabdominal sepsis, and acute lung injury, and a promising therapeutic target of severe sepsis. We sought to investigate the effect of antibodies to HMGB1 on severe sepsis in a rat cecal ligation and puncture (CLP) model.
  
  
  METHODS
  Adult male Sprague-Dawley rats underwent CLP and then were randomly divided into two groups: treatment with anti-HMGB1 polyclonal antibodies, and non-immune IgG-treated controls. The serum HMGB1 concentrations were measured at ten time points (preoperatively, and postoperatively at 4, 8, 20, 32, and 48 h and at 3, 4, 5, and 6 days). Hematoxylin-eosin staining, elastica-Masson staining, and immunohistochemical staining for HMGB1 were performed on the cecum and the lung to assess pathological changes 24 h after the CLP procedure.
  
  
  RESULTS
  Treatment with anti-HMGB1 antibodies significantly increased survival [55% (anti-HMGB1) vs. 9% (controls); P< 0.01]. The serum HMGB1 concentrations at postoperative hours 20 and 32 of the anti-HMGB1 antibody-treated animals were significantly lower than those of the controls (P < 0.05). Treatment with anti-HMGB1 antibodies markedly diminished the pathological changes and the number of HMGB1-positive cells in the cecum and the lung.
  
  
  CONCLUSIONS
  The present study demonstrates that anti-HMGB1 antibodies are effective in the treatment of severe sepsis in a rat model, thereby supporting the relevance of HMGB1 eradication therapy for severe sepsis.
authors.affiliation: Department of Surgery, School of Medicine, Keio University, Shinanomachi 35, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Soji
authors.initials: S
authors.lastname: Ozawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saikawa
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ueda
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukata
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D002432:Cecum / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D024243:HMGB1 Protein; D006609:High Mobility Group Proteins / Q000097:blood / Q000276:immunology*; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D009500:Neutralization Tests; D010538:Peritonitis / Q000276:immunology* / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins / Q000097:blood / Q000276:immunology*; D018805:Sepsis / Q000628:therapy*
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D006609:High Mobility Group Proteins; D012097:Repressor Proteins