title: Spillover of cytokines and reactive oxygen species in ventilator-induced lung injury associated with inflammation and apoptosis in distal organs.
abstract: BACKGROUND
  The mechanism between ventilator-induced lung injury (VILI) and multiple organ injury is unclear. The aim of our study was to investigate the mechanisms of VILI-induced distal organ injury.
  
  
  METHODS
  VILI was induced in rat lungs with high tidal volume (V(T)) ventilation of 40 mL/kg for 6 h. Rats with low V(T) ventilation of 6 mL/kg served as controls. Inflammatory and apoptotic indices in lung and distal organs were assessed.
  
  
  RESULTS
  VILI increased lung weight, airway pressure, inflammation, and apoptotic pathologic changes without hemodynamic changes. The white blood cell count and the levels of H2O2, interleukin-1β (IL-1β), tumor necrosis factor alpha, and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid were higher in the VILI group compared with the control group. H2O2, IL-1β, and tumor necrosis factor alpha in blood from the left ventricle were up-regulated. H2O2, IL-1β, tumor necrosis factor alpha, macrophage inflammatory protein-2, c-Jun N-terminal kinase, p38, nuclear factor kappa B, and caspase-3 in lung, heart, liver, and kidney tissues in the VILI group were up-regulated. Furthermore, the apoptotic score for the kidneys was higher than those for other distal organs in the VILI group.
  
  
  CONCLUSIONS
  High V(T) ventilation induces VILI and is associated with inflammation and apoptosis in distal organs. Up-regulation of reactive oxygen species and cytokines in VILI is associated with systemic inflammatory responses. Kidney tissue appears to be more vulnerable than heart and liver tissues following VILI.
authors: Section of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Institute of Clinical Medicine.
authors: Yung-Yang
authors: YY
authors: Liu
authors: Section of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Institute of Emergency and Critical Care Medicine and the Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan. Department of Medicine, National Defense Medical Center, Taipei, Taiwan. chiang01@vghtpe.gov.tw chiang1990@gmail.com.
authors: Chi-Huei
authors: CH
authors: Chiang
authors: Section of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Chiao-Hui
authors: CH
authors: Chuang
authors: Section of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Shiou-Ling
authors: SL
authors: Liu
authors: Section of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Yi-Han
authors: YH
authors: Jheng
authors: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
authors: Jay H
authors: JH
authors: Ryu
mesh_terms: D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053148:Caspase 3 / Q000032:analysis; D054426:Chemokine CXCL2 / Q000032:analysis*; D053583:Interleukin-1beta / Q000032:analysis* / Q000097:blood; D053612:Janus Kinases / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008168:Lung / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology; D016328:NF-kappa B / Q000032:analysis; D010766:Phosphorylation; D011654:Pulmonary Edema / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D015854:Up-Regulation; D055397:Ventilator-Induced Lung Injury / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D054426:Chemokine CXCL2; D053583:Interleukin-1beta; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D053612:Janus Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: apoptosis; inflammation; reactive oxygen species; ventilator-induced lung injury