This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200401-023OCv1 170/6/613    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dolinay, T. Articles by Choi, A. M. K. Search for Related Content PubMed PubMed Citation Articles by Dolinay, T. Articles by Choi, A. M. K.

Inhaled Carbon Monoxide Confers Antiinflammatory Effects against Ventilator-induced Lung Injury

Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Pulmonary Medicine, University of Debrecen, Debrecen, Hungary; and Thoracic Surgery Research Laboratory, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada

Correspondence and requests for reprints should be addressed to Augustine M. K. Choi, M.D., Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15213. E-mail: choiam{at}upmc.edu

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- 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-B pathways. Our data lead to a tempting speculation that inhaled CO might be useful in minimizing VILI.

Key Words: cytokines • heme oxygenase-1 • p38 MAPK

This article has been cited by other articles:

				A. Hoetzel, T. Dolinay, S. Vallbracht, Y. Zhang, H. P. Kim, E. Ifedigbo, S. Alber, A. M. Kaynar, R. Schmidt, S. W. Ryter, et al. Carbon Monoxide Protects against Ventilator-induced Lung Injury via PPAR-{gamma} and Inhibition of Egr-1 Am. J. Respir. Crit. Care Med., June 1, 2008; 177(11): 1223 - 1232. [Abstract] [Full Text] [PDF]

				J. A. Nemzek, C. Fry, and O. Abatan Low-dose carbon monoxide treatment attenuates early pulmonary neutrophil recruitment after acid aspiration Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L644 - L653. [Abstract] [Full Text] [PDF]

				S. W. Ryter, D. Morse, and A. M. K. Choi Carbon Monoxide and Bilirubin: Potential Therapies for Pulmonary/Vascular Injury and Disease Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 175 - 182. [Abstract] [Full Text] [PDF]

				T. Dolinay, N. Kaminski, M. Felgendreher, H. P. Kim, P. Reynolds, S. C. Watkins, D. Karp, S. Uhlig, and A. M. K. Choi Gene expression profiling of target genes in ventilator-induced lung injury Physiol Genomics, September 14, 2006; 26(1): 68 - 75. [Abstract] [Full Text] [PDF]

				G. Y. Suh, Y. Jin, A.-K. Yi, X. M. Wang, and A. M. K. Choi CCAAT/Enhancer-Binding Protein Mediates Carbon Monoxide-Induced Suppression of Cyclooxygenase-2 Am. J. Respir. Cell Mol. Biol., August 1, 2006; 35(2): 220 - 226. [Abstract] [Full Text] [PDF]

				S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]

				Y. Jin and A. M. K. Choi Cytoprotection of Heme Oxygenase-1/Carbon Monoxide in Lung Injury Proceedings of the ATS, October 1, 2005; 2(3): 232 - 235. [Abstract] [Full Text] [PDF]

				D. Morse and A. M. K. Choi Heme Oxygenase-1: From Bench to Bedside Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 660 - 670. [Abstract] [Full Text] [PDF]

				S. R. Thom, L. K. Weaver, and N. B. Hampson "Therapeutic" Carbon Monoxide May Be Toxic Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1318 - 1318. [Full Text] [PDF]

				A. M.K. Choi and T. Dolinay Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1318 - 1319. [Full Text] [PDF]

				S. Ghosh, M. R. Wilson, S. Choudhury, H. Yamamoto, M. E. Goddard, B. Falusi, N. Marczin, and M. Takata Effects of inhaled carbon monoxide on acute lung injury in mice Am J Physiol Lung Cell Mol Physiol, June 1, 2005; 288(6): L1003 - L1009. [Abstract] [Full Text] [PDF]

				D. Angus, A. Ishizaka, M. Matthay, F. Lemaire, W. MacNee, and E. Abraham Critical Care in AJRCCM 2004 Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 537 - 544. [Full Text] [PDF]