Abstract
Inflammation and immunity result in a wide range of disease processes, including atherosclerosis, vascular thrombosis and sepsis. Heme oxygenase-1 (HO-1) is a key enzyme that is integral to the temporal and spatial regulation of the host response and, together with its products carbon monoxide (CO) and bilirubin, is crucial for maintaining homeostasis and the preservation of function and life. An increasing number of reports demonstrates that HO-1, CO and bilirubin regulate the immune response. As CO and bilirubin enter clinical trials, there are obstacles to be addressed before their full therapeutic potential can be achieved. In this article, we delineate the challenges that lie ahead regarding toxicity, pharmacokinetics and mechanisms of action to be able to take full advantage of the powerful cytoprotective properties of these agents for clinical benefit.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Atherosclerosis / physiopathology
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Bilirubin / adverse effects
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Bilirubin / pharmacokinetics
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Bilirubin / pharmacology*
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Bilirubin / therapeutic use
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Biliverdine / pharmacology*
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Biliverdine / therapeutic use
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Carbon Monoxide / adverse effects
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Carbon Monoxide / pharmacokinetics
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Carbon Monoxide / pharmacology*
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Carbon Monoxide / therapeutic use
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Cytoprotection / drug effects
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Heme Oxygenase-1 / metabolism*
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Heme Oxygenase-1 / physiology
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Homeostasis / drug effects
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Homeostasis / physiology
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Humans
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Protective Agents / adverse effects
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Protective Agents / pharmacokinetics
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Protective Agents / pharmacology*
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Protective Agents / therapeutic use
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Sepsis / physiopathology
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Thrombosis / physiopathology
Substances
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Protective Agents
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Carbon Monoxide
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Heme Oxygenase-1
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Biliverdine
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Bilirubin