Spillover of cytokines and reactive oxygen species in ventilator-induced lung injury associated with inflammation and apoptosis in distal organs

Respir Care. 2014 Sep;59(9):1422-32. doi: 10.4187/respcare.02992. Epub 2014 Jul 22.

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.

Keywords: apoptosis; inflammation; reactive oxygen species; ventilator-induced lung injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bronchoalveolar Lavage Fluid / chemistry
  • Caspase 3 / analysis
  • Chemokine CXCL2 / analysis*
  • Interleukin-1beta / analysis*
  • Interleukin-1beta / blood
  • Janus Kinases / metabolism
  • Kidney / chemistry
  • Kidney / enzymology
  • Liver / chemistry
  • Liver / enzymology
  • Lung / chemistry
  • Lung / enzymology
  • Lung / pathology
  • Male
  • Myocardium / chemistry
  • Myocardium / enzymology
  • NF-kappa B / analysis
  • Phosphorylation
  • Pulmonary Edema / etiology
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / analysis
  • Tumor Necrosis Factor-alpha / analysis*
  • Up-Regulation
  • Ventilator-Induced Lung Injury / complications
  • Ventilator-Induced Lung Injury / metabolism*
  • Ventilator-Induced Lung Injury / pathology
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemokine CXCL2
  • Interleukin-1beta
  • NF-kappa B
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Janus Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Caspase 3