Carbon monoxide in sepsis.
Despite modern practices in critical care medicine, sepsis or systemic inflammatory response syndrome remains a leading cause of morbidity and mortality in the intensive care unit. Thus, the need to identify new therapeutic tools for the treatment of sepsis is urgent. In this context, carbon monoxide has become a promising therapeutic molecule that can potentially prevent uncontrolled inflammation in sepsis. In humans, carbon monoxide arises endogenously from the degradation of heme by heme oxygenase enzymes. Both endogenously synthesized and exogenously applied carbon monoxide can exert antiinflammatory and antiapoptotic effects in cells and tissues. Based on these properties, carbon monoxide, when applied at low concentration, conferred protection in a variety of cellular and rodent models of sepsis, and furthermore reduced morbidity and mortality in vivo. Therefore, application of carbon monoxide may have a major impact on the future of sepsis treatment. This review summarizes evidence for salutary effects of carbon monoxide in sepsis of various organs, including lung, heart, kidney, liver, and intestine, and discusses the potential translation of the data into human clinical trials.
Hoetzel
Alexander
A
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, MUH 628 NW, 3459 Fifth Ave, Pittsburgh, Pennsylvania 15213, USA.
Dolinay
Tamas
T
Schmidt
Rene
R
Choi
Augustine M K
AM
Ryter
Stefan W
SW
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005544:Forecasting; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D014652:Vascular Diseases / Q000188:drug therapy