title: Heparin-binding epidermal growth factor-like growth factor attenuates acute lung injury and multiorgan dysfunction after scald burn.
abstract: BACKGROUND
  Impaired gut barrier function and acute lung injury (ALI) are significant components of the multiorgan dysfunction syndrome that accompanies severe burns. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been shown to reduce inflammation, preserve gut barrier function, and protect the lungs from acute injury in several models of intestinal injury; however, comparable effects of HB-EGF after burn injury have never been investigated. The present studies were based on the hypothesis that HB-EGF would reduce the severity of ALI and multiorgan dysfunction after scald burns in mice.
  
  
  METHODS
  Mice were randomized to sham, burn (25% of total body surface area with full thickness dorsal scald), and burn + HB-EGF groups. The HB-EGF group was pretreated with two enteral doses of HB-EGF (1200 μg/kg/dose). Mice were resuscitated after injury and sacrificed at 8 h later. Their lungs were harvested for determination of pulmonary myeloperoxidase activity, wet:dry ratios, and terminal deoxynucleotidyl transferase dUTP nick end label and cleaved caspase 3 immunohistochemistry. Lung function was assessed using the SCIREQ Flexivent. Splenic apoptosis was quantified by Western blot for cleaved caspase 3, and intestinal permeability was measured using the everted gut sac method.
  
  
  RESULTS
  Mice subjected to scald burn injury had increased lung myeloperoxidase levels, increased pulmonary and splenic apoptosis, elevated airway resistance and bronchial reactivity, and increased intestinal permeability compared with sham mice. These abnormalities were significantly attenuated in mice that were subjected to scald burn injury but treated with enteral HB-EGF.
  
  
  CONCLUSIONS
  These data suggest that HB-EGF protects mice from ALI after scald burn and attenuates the severity of postburn multiorgan dysfunction.
authors.affiliation: Division of Pediatric Critical Care Medicine, Nationwide Children's Hospital, Columbus, Ohio; Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio. Electronic address: jeffrey.lutmer@nationwidechildrens.org.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lutmer
authors.forename: Daniel
authors.initials: D
authors.lastname: Watkins
authors.forename: Chun-Liang
authors.initials: CL
authors.lastname: Chen
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.forename: Gail
authors.initials: G
authors.lastname: Besner
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D011897:Random Allocation; D012720:Severity of Illness Index; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D009195:Peroxidase
keywords: Acute lung injury; Heparin-binding epidermal growth factor–like growth factor; Multiorgan dysfunction syndrome