Carbon Monoxide Relieves Chronic Colitis in Mice
Researchers identify signaling pathway that may lead to new therapies for humans with ulcerative colitis
TUESDAY, Dec. 20 (HealthDay News) -- Inhaled carbon monoxide (CO) relieves symptoms of chronic colitis in mice, which may explain why cigarette smoking protects against ulcerative colitis in humans, according to a study published online Dec. 19 in the Journal of Experimental Medicine.
Scott Plevy, M.D., of the University of Pittsburgh, and colleagues studied the effects of CO on 20 mice with established chronic colitis. Twelve of the mice received 250 parts per million CO from eight to 12 weeks of age while eight control mice were exposed to ambient air.
The researchers found that CO significantly reduced chronic mucosal inflammation that is similar to ulcerative colitis in humans. They demonstrated that the immunologic and therapeutic effects of CO are dependent on a previously unidentified signaling pathway involving heme oxygenase-1 (HO-1). The results suggest that CO alters interferon-gamma signaling, and that CO and HO-1 deviate an immune response away from a T helper-1 profile toward an anti-inflammatory response.
"This study may have important implications in human inflammatory bowel disease," the authors conclude. "First, therapeutic strategies designed to induce HO-1 may eliminate toxicity concerns associated with direct administration of CO. Future experiments will further characterize metabolic products and enzymes in the HO-1 pathway as well as HO-1-inducing agents for immunologic actions in inflammatory bowel disease models."