Contribution of high-mobility group box-1 to the development of ventilator-induced lung injury.
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.
Ogawa
Eileen N
EN
Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Ishizaka
Akitoshi
A
Tasaka
Sadatomo
S
Koh
Hidefumi
H
Ueno
Hiroshi
H
Amaya
Fumimasa
F
Ebina
Masahito
M
Yamada
Shingo
S
Funakoshi
Yosuke
Y
Soejima
Junko
J
Moriyama
Kiyoshi
K
Kotani
Toru
T
Hashimoto
Satoru
S
Morisaki
Hiroshi
H
Abraham
Edward
E
Takeda
Junzo
J
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
D024243:HMGB1 Protein; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha