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

Yung Yang Liu, Chi Huei Chiang, Chiao Hui Chuang, Shiou Ling Liu, Yi Han Jheng, Jay H Ryu

Research output: Contribution to journalArticle

12 Scopus citations


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<inf>T</inf>) ventilation of 40 mL/kg for 6 h. Rats with low V<inf>T</inf> 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 H<inf>2</inf>O<inf>2</inf>, 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. H<inf>2</inf>O<inf>2</inf>, IL-1β, and tumor necrosis factor alpha in blood from the left ventricle were up-regulated. H<inf>2</inf>O<inf>2</inf>, 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<inf>T</inf> 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.

Original languageEnglish (US)
Pages (from-to)1422-1432
Number of pages11
JournalRespiratory Care
Issue number9
StatePublished - 2014



  • Apoptosis
  • Inflammation
  • Reactive oxygen species
  • Ventilator-induced lung injury

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this