Interleukin-6 mediates pulmonary vascular permeability in a two-hit model of ventilator-associated lung injury

Ozlem U. Gurkan, Chaoxia He, Rachel Zielinski, Hamid Rabb, Landon S. King, Jeffrey M. Dodd-O, Franco R. D'Alessio, Neil Aggarwal, David Pearse, Patrice M. Becker

Research output: Contribution to journalArticlepeer-review

Abstract

To test the hypothesis that interleukin-6 (IL-6) contributes to the development of ventilator-associated lung injury (VALI), IL-6deficient (IL6 -/) and wild-type control (WT) mice received intratracheal hydrochloric acid followed by randomization to mechanical ventilation (MV + IT HCl) or spontaneous ventilation (IT HCl). After 4 hours, injury was assessed by estimation of lung lavage protein concentration and total and differential cell counts, wet/dry lung weight ratio, pulmonary cell death, histologic inflammation score (LIS), and parenchymal myeloperoxidase (MPO) concentration. Vascular endothelial growth factor (VEGF) concentration was measured in lung lavage and homogenate, as IL-6 and stretch both regulate expression of this potent mediator of permeability. MV-induced increases in alveolar barrier dysfunction and lavage VEGF were attenuated in IL6 -/- mice as compared with WT controls, whereas tissue VEGF concentration increased. The effects of IL-6 deletion on alveolar permeability and VEGF concentration were inflammation independent, as parenchymal MPO concentration, LIS, and lavage total and differential cell counts did not differ between WT and IL6 -/- mice following MV + IT HCl. These data support a role for IL-6 in promoting VALI in this two-hit model. Strategies to interfere with IL-6 expression or signaling may represent important therapeutic targets to limit the injurious effects of MV in inflamed lungs.

Original languageEnglish (US)
Pages (from-to)575-584
Number of pages10
JournalExperimental Lung Research
Volume37
Issue number10
DOIs
StatePublished - Dec 2011

Keywords

  • Acid aspiration
  • Mechanical ventilation
  • Pulmonary barrier dysfunction
  • Vascular endothelial growth factor (VEGF)

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry

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