title: Hemopexin in severe inflammation and infection: mouse models and human diseases.
abstract: BACKGROUND
  Cell-free plasma hemoglobin is associated with poor outcome in patients with sepsis. Extracellular hemoglobin and secondarily released heme amplify inflammation in the presence of microbial TLR ligands and/or endogenous mediators. Hemopexin, a plasma protein that binds heme with extraordinary affinity, blocks these effects and has been proposed as a possible treatment approach to decrease inflammation in critically ill patients.
  
  
  METHODS
  We studied mouse models of endotoxemia, burn wound infections and peritonitis in order to assess if a repletion strategy for hemopexin might be reasonable. We also measured hemopexin in small numbers of three patient populations that might be logical groups for hemopexin therapy: patients with sepsis and ARDS, patients with severe burns, and premature infants.
  
  
  RESULTS
  Despite severe disease, mean plasma hemopexin levels were increased above baseline in each murine model. However, plasma hemopexin levels were decreased or markedly decreased in many patients in each of the three patient populations.
  
  
  CONCLUSIONS
  Potentially different behavior of hemopexin in mice and humans may be important to consider when utilizing murine models to represent acute human inflammatory diseases in which heme plays a role. The findings raise the possibility that decreased hemopexin could result in insufficiently neutralized or cleared heme in some patients with ARDS, burns, or in premature infants who might be candidates to benefit from hemopexin administration.
authors.affiliation: Department of Pediatrics, Infectious Disease Unit, Massachusetts General Hospital, and Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA. tlin7@mgh.harvard.edu.
authors.forename: Tian
authors.initials: T
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, Infectious Disease Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA. dramaitad@gmail.com.
authors.forename: Dayana
authors.initials: D
authors.lastname: Maita
authors.affiliation: Department of Pediatrics, Infectious Disease Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA. sthundivalappil@mgh.harvard.edu.
authors.forename: Sujatha R
authors.initials: SR
authors.lastname: Thundivalappil
authors.affiliation: Department of Pediatrics, Infectious Disease Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA. friley@mgh.harvard.edu.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Riley
authors.affiliation: Department of Pediatrics, Infectious Disease Unit, Massachusetts General Hospital, 149 13th Street, Charlestown, MA, 02129, USA. Jasmin.Hambsch@umm.de.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Hambsch
authors.affiliation: Department of Pediatric Newborn Medicine at Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. lvanmarter@partners.org.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Marter
authors.affiliation: Department of Pediatric Newborn Medicine at Brigham and Women's Hospital, and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA. hchristou@partners.org.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Christou
authors.affiliation: Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. lberra@mgh.harvard.edu.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Berra
authors.affiliation: Department of Surgery, MGH Burn Service, Massachusetts General Hospital, and Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA. shawn.fagan@jmsburncenters.com.
authors.forename: Shawn
authors.initials: S
authors.lastname: Fagan
authors.affiliation: Department of Medicine, Pulmonary and Critical Care Medicine, Massachusetts General Hospital, and Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA. Christiani.David@mgh.harvard.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.affiliation: Department of Pediatrics and Medicine, Infectious Disease Unit, Massachusetts General Hospital, and Harvard Medical School, 149 13th Street, Charlestown, MA, 02129, USA. warren@helix.mgh.harvard.edu.
authors.forename: H Shaw
authors.initials: HS
authors.lastname: Warren
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002056:Burns / Q000097:blood* / Q000175:diagnosis; D004195:Disease Models, Animal; D005260:Female; D006466:Hemopexin / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006466:Hemopexin