Inhaled carbon monoxide confers antiinflammatory effects against ventilator-induced lung injury.
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-alpha 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-kappaB pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI.
Dolinay
Tamás
T
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Szilasi
Mária
M
Liu
Mingyao
M
Choi
Augustine M K
AM
D000280:Administration, Inhalation; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002248:Carbon Monoxide / Q000008:administration & dosage*; D016207:Cytokines / Q000032:analysis; D004926:Escherichia coli; D006360:Heat-Shock Proteins / Q000032:analysis; D006419:Heme Oxygenase (Decyclizing); D008070:Lipopolysaccharides / Q000009:adverse effects; D008171:Lung Diseases / Q000209:etiology / Q000382:microbiology / Q000628:therapy*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D023421:Models, Animal; D010105:Oxygenases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D002248:Carbon Monoxide; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases