Carbon monoxide attenuates aeroallergen-induced inflammation in mice.
Carbon monoxide (CO) generated by catalysis of heme by heme oxygenase is increased in the exhaled air of asthmatic patients. Based on recent studies demonstrating that asthma is an inflammatory disease associated with increased oxidants and that CO confers cytoprotection in oxidant-induced lung injury and inflammation, we sought to better understand the functional role of CO in asthma by using an aeroallergen model. Mice were sensitized to ovalbumin, challenged with aerosolized ovalbumin, and maintained in either CO (250 parts/million) or room air for 48 h. The differential effects of CO on bronchoalveolar lavage (BAL) fluid cell types were observed, with a marked attenuation of BAL fluid eosinophils in the CO-treated animals at 24 and 48 h. A marked reduction of the proinflammatory cytokine interleukin-5 was observed in the CO-treated mice, with no significant changes for other proinflammatory cytokines. These differential effects of CO were also observed with leukotrienes (LTs) and prostaglandins in that CO significantly decreased BAL fluid PGE2, and LTB4 but exerted negligible effect on thromboxane B2 or LTC4/D4/E4. Our data suggest a putative immunoregulatory role for CO in aeroallergen-induced inflammation in mice.
Chapman
J T
JT
Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Otterbein
L E
LE
Elias
J A
JA
Choi
A M
AM
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000517:prevention & control*; D001773:Blood Cells / Q000187:drug effects / Q000473:pathology; D001853:Bone Marrow / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002248:Carbon Monoxide / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D015777:Eicosanoids; D018836:Inflammation Mediators; D007975:Leukotriene B4; D002248:Carbon Monoxide; D010047:Ovalbumin; D015232:Dinoprostone