title: Ventilator-induced injury augments interleukin-1beta production and neutrophil sequestration in lipopolysaccharide-treated lungs.
abstract: Mechanical ventilators are commonly used to support critically ill patients; however, inappropriate ventilator settings might initiate or augment lung injury. To determine whether a large tidal volume (Vt) augments inflammatory responses and neutrophil sequestration in the lungs of rats receiving intratracheal lipopolysaccharides (LPS). Rats received intratracheal instillation of LPS (0.5 mg/kg) followed by 4 h of mechanical ventilation (MV) at 60 strokes per min with a Vt of 10 mL/kg as control MV, or 30 strokes per min with a Vt of 20 mL/kg of body weight as high-volume MV (HMV). In addition, monoclonal antibodies against rat intercellular adhesion molecule 1 (ICAM-1) or immunoglobulin G (50 mg/kg) were administered 30 min before LPS instillation and MV. Our study demonstrates that HMV enhances pulmonary permeability and induces neutrophil recruitment into the alveolar space and pulmonary edema. Intratracheal instillation of LPS caused marked lung injury, neutrophil recruitment, and production of cytokines and chemokines. Combining LPS instillation and HMV synergistically upregulated interleukin 1beta (IL-1beta) production and neutrophil sequestration in lung tissues. The ICAM-1 expression in lung tissues was responsible for the synergistic effects of neutrophil sequestration. Synergistic upregulation of IL-1beta production and neutrophil sequestration was attenuated by blocking ICAM-1 by neutralizing antibody pretreatment. High Vt MV in LPS-injured lung causes synergistic production of IL-1beta and sequestration of neutrophil via ICAM-1-dependent effects.
authors.affiliation: Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan.
authors.forename: Shu-Min
authors.initials: SM
authors.lastname: Lin
authors.forename: Horng-Chyuan
authors.initials: HC
authors.lastname: Lin
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.forename: Chien-Da
authors.initials: CD
authors.lastname: Huang
authors.forename: Chien-Ying
authors.initials: CY
authors.lastname: Liu
authors.forename: Chun-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Han-Pin
authors.initials: HP
authors.lastname: Kuo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D039481:CD11b Antigen / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D039481:CD11b Antigen; D054426:Chemokine CXCL2; D018925:Chemokines; C513296:Cxcl2 protein, rat; D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1