Carbon monoxide in the treatment of sepsis.
Carbon monoxide (CO), a low-molecular-weight gas, is endogenously produced in the body as a product of heme degradation catalyzed by heme oxygenase (HO) enzymes. As the beneficial roles of HO system have been elucidated in vitro and in vivo, CO itself has also been reported as a potent cytoprotective molecule. Whereas CO represents a toxic inhalation hazard at high concentration, low-dose exogenous CO treatment (~250-500 parts per million) demonstrates protective functions including but not limited to the anti-inflammatory and antiapoptotic effects in preclinical models of human diseases. Of note, CO exposure confers protection in animal models of sepsis by inhibiting inflammatory responses and also enhancing bacterial phagocytosis in leukocytes. These unique functions of CO including both dampening inflammation and promoting host defense mechanism are mediated by multiple pathways such as autophagy induction or biosynthesis of specialized proresolving lipid mediators. We suggest that CO gas may represent a novel therapy for patients with sepsis.
Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, New York; and Division of Pulmonary and Crit Care Medicine, Weill Cornell Medical College, New York, New York.
Kiichi
K
Nakahira
Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, New York; and Division of Pulmonary and Crit Care Medicine, Weill Cornell Medical College, New York, New York amchoi@med.cornell.edu.
Augustine M K
AM
Choi
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D002248:Carbon Monoxide / Q000494:pharmacology* / Q000627:therapeutic use*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)
carbon monoxide; clinical trial; sepsis