title: Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury.
abstract: BACKGROUND
  Proinflammatory cytokines play an important role in ventilator-induced lung injury (VILI). High-mobility group box-1 (HMGB1) is a macrophage-derived proinflammatory cytokine that can cause lung injury.
  
  
  OBJECTIVE
  This study tested the hypothesis that HMGB1 is released in intact lungs ventilated with large Vt. A second objective was to identify the source of HMGB1. A third objective was to examine the effects of blocking HMGB1 on the subsequent development of VILI.
  
  
  METHODS
  Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained from rabbits mechanically ventilated for 4 h with a small (8 ml/kg) versus a large (30 ml/kg) Vt. BALF was also obtained from rabbits with intratracheal instillation of anti-HMGB1 antibody before the initiation of large Vt ventilation.
  
  
  RESULTS
  The concentrations of HMGB1 in BALF were fivefold higher in the large than in the small Vt group. Immunohistochemistry and immunofluorescence studies revealed expression of HMGB1 in the cytoplasm of macrophages and neutrophils in lungs ventilated with large Vt. Blocking HMGB1 improved oxygenation, limited microvascular permeability and neutrophil influx into the alveolar lumen, and decreased concentrations of tumor necrosis factor-alpha in BALF.
  
  
  CONCLUSIONS
  These observations suggest that HMGB1 could be one of the deteriorating factors in the development of VILI.
authors.affiliation: Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Eileen N
authors.initials: EN
authors.lastname: Ogawa
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Ishizaka
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Tasaka
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Koh
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueno
authors.forename: Fumimasa
authors.initials: F
authors.lastname: Amaya
authors.forename: Masahito
authors.initials: M
authors.lastname: Ebina
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Funakoshi
authors.forename: Junko
authors.initials: J
authors.lastname: Soejima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Moriyama
authors.forename: Toru
authors.initials: T
authors.lastname: Kotani
authors.forename: Satoru
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morisaki
authors.forename: Edward
authors.initials: E
authors.lastname: Abraham
authors.forename: Junzo
authors.initials: J
authors.lastname: Takeda
mesh_terms: D001992:Bronchoalveolar Lavage Fluid; D002463:Cell Membrane Permeability / Q000502:physiology; D024243:HMGB1 Protein / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000502:physiology; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D024243:HMGB1 Protein; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha