Carbon monoxide attenuates aero allergen-induced inflammation in mice

Carbon monoxide (CO) generated by catalysis of heme by heme oxygenase is in creased in the exhaled air of asthmatic patients. Based on recent studies d emonstrating that asthma is an inflammatory disease associated with increas ed oxidants and that CO confers cytoprotection in oxidant-induced lung inju ry and inflammation, we sought to better understand the functional role of CO in asthma by using an aeroallergen model. Mice were sensitized to ovalbu min, challenged with aerosolized ovalbumin, and maintained in either CO (25 0 parts/million) or room air for 48 h. The differential effects of CO on br onchoalveolar lavage (BAL) fluid cell types were observed, with a marked at tenuation of BAL fluid eosinophils in the CO-treated animals at 24 and 48 h . A marked reduction of the proinflammatory cytokine interleukin-5 was obse rved in the CO-treated mice, with no significant changes for other proinfla mmatory cytokines. These differential Effects of CO were also observed with leukotrienes (LTs) and prostaglandins in that CO significantly decreased B AL fluid PGE(2), and LTB4 but exerted negligible effect on thromboxane B-2 or LTC4/D-4/E-4. Our data suggest a putative immunoregulatory role for CO i n aeroallergen-induced inflammation in mice.