In This Issue

CO gives sepsis the heave-HO(-1)The inflammatory phase of sepsis, characterized by a systemic response to infection, has life-threatening effects if left unchecked.However, therapies aimed at limiting inflammation have had little success and have the potential to hamper the antimicrobial immune response.In this issue (pages 239-247), Chung and colleagues have identified CO, generated by heme oxygenase-1 (HO-1), as a natural mediator of mouse host defense against sepsis-causing infections that does not modify the inflammatory response, making it a potential therapeutic for the treatment of individuals with sepsis.HO-1-deficient mice were more susceptible to the lethal effects of polymicrobial sepsis induced by cecal ligation and puncture (CLP) than were WT mice.In contrast, mice overexpressing human HO-1 (hHO-1) in vascular SMCs and intestinal myofibroblasts showed increased survival following CLP compared with WT mice.More specific analysis indicated that overexpression of hHO-1 did not alter the inflammatory response, but it did increase neutrophil phagocytosis of Enterococcus faecalis bacteria.Further studies demonstrated that HO-1-deficient mice administered a COreleasing molecule did not show increased susceptibility to the lethal effects of CLP-induced sepsis and, more clinically relevant, WT mice administered the CO-releasing molecule after the onset of CLP-induced sepsis showed improved survival.