title: Therapeutic applications of carbon monoxide.
abstract: Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models.
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC-441 South, P.O. Box 208057, New Haven, CT 06520-8057, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Knauert
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC-441 South, P.O. Box 208057, New Haven, CT 06520-8057, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Vangala
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC-441 South, P.O. Box 208057, New Haven, CT 06520-8057, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Haslip
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale University School of Medicine, 300 Cedar Street, TAC-441 South, P.O. Box 208057, New Haven, CT 06520-8057, USA.
authors.forename: Patty J
authors.initials: PJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D006801:Humans
chemical_list: D002248:Carbon Monoxide