Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury

Tamás Dolinay, Mária Szilasi, Mingyao Liu, Augustine M.K. Choi

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

Ventilator-induced lung injury (VILI) is a major cause of morbidity and mortality in intensive care units. The stress-inducible gene product, heme oxygenase-1, and carbon monoxide (CO), a major by-product of heme oxygenase catalysis of heme, have been shown to confer potent antiinflammatory effects in models of tissue and cellular injury. In this study, we observed increased expression of heme oxygenase-1 mRNA and protein in a rat model of VILI. To assess the physiologic function of heme oxygenase-1 induction in VILI, we determined whether low concentration of inhaled CO could serve to protect the lung against VILI. Low concentration of inhaled CO significantly reduced tumor necrosis factor-α levels and total cell count in lavage fluid, while simultaneously elevating levels of antiinflammatory interleukin-10 levels. To better characterize the mechanism of CO-mediated antiinflammatory effects, we examined key signaling pathways, which may mediate CO-induced antiinflammatory effects. We demonstrate that inhaled CO exerts antiinflammatory effects in VILI via the p38 mitogen-activated protein kinase pathway but independent of activator protein-1 and nuclear factor-κB pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI.

Original languageEnglish (US)
Pages (from-to)613-620
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume170
Issue number6
DOIs
StatePublished - Sep 15 2004

Keywords

  • Cytokines
  • Heme oxygenase-1
  • p38 MAPK

ASJC Scopus subject areas

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

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