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 cytoprotectiv...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2015-12, Vol.309 (12), p.L1387-L1393
Main Authors: Nakahira, Kiichi, Choi, Augustine M K
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Anti-Inflammatory Agents - therapeutic use
Biosynthesis
Carbon monoxide
Carbon Monoxide - pharmacology
Carbon Monoxide - therapeutic use
Heme Oxygenase (Decyclizing) - metabolism
Humans
Inflammation - drug therapy
Inflammation - metabolism
Medical treatment
Molecular weight
Physiology
Sepsis
Sepsis - drug therapy
Sepsis - metabolism
Signal Transduction - drug effects
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Summary: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.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00311.2015