Therapeutic applications of carbon monoxide in lung disease.

Carbon monoxide (CO) offers potential therapeutic avenues in the treatment of lung disorders. CO arises endogenously from heme degradation, catalyzed by the heme oxygenase enzymes. In cell culture, CO exerts potent anti-inflammatory, anti-apoptotic and anti-proliferative effects by modulating intracellular signaling pathways. In vivo, CO confers tissue protection in animal models of lung disease, including those with oxidative and inflammatory lung injury and ischemia/reperfusion injury. Furthermore, low-dose CO ameliorates vascular injury and reduces the rejection rate of lung and vascular grafts. Recent advances include the observation that CO protects the lung in models of bleomycin-induced lung fibrosis and ventilator-induced lung injury. Despite the success of CO therapy in animal models, the utility of CO as therapy in humans remains uncertain.