title: Cecal ligation and puncture-induced murine sepsis does not cause lung injury.
abstract: OBJECTIVE
  The cause of death in murine models of sepsis remains unclear. The primary purpose of this study was to determine if significant lung injury develops in mice predicted to die after cecal ligation and puncture-induced sepsis compared with those predicted to live.
  
  
  METHODS
  Prospective, laboratory controlled experiments.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Adult, female, outbred Institute of Cancer Research mice.
  
  
  METHODS
  Mice underwent cecal ligation and puncture to induce sepsis. Two groups of mice were euthanized at 24 and 48 hrs postcecal ligation and puncture and samples were collected. These mice were further stratified into groups predicted to die (Die-P) and predicted to live (Live-P) based on plasma interleukin-6 levels obtained 24 hrs postcecal ligation and puncture. Multiple measures of lung inflammation and lung injury were quantified in these two groups. Results from a group of mice receiving intratracheal normal saline without surgical intervention were also included as a negative control. As a positive control, bacterial pneumonia was induced with Pseudomonas aeruginosa to cause definitive lung injury. Separate mice were followed for survival until Day 28 postcecal ligation and puncture. These mice were used to verify the interleukin-6 cutoffs for survival prediction.
  
  
  RESULTS
  After sepsis, both the Die-P and Live-P mice had significantly suppressed measures of respiratory physiology but maintained normal levels of arterial oxygen saturation. Bronchoalveolar lavage levels of pro- and anti-inflammatory cytokines were not elevated in the Die-P mice compared with the Live-P. In addition, there was no increase in the recruitment of neutrophils to the lung, pulmonary vascular permeability, or histological evidence of damage. In contrast, all of these pulmonary injury and inflammatory parameters were increased in mice with Pseudomonas pneumonia.
  
  
  CONCLUSIONS
  These data demonstrate that mice predicted to die during sepsis have no significant lung injury. In murine intra-abdominal sepsis, pulmonary injury cannot be considered the etiology of death in the acute phase.
authors.affiliation: Department of Surgery, Boston University Medical Center, Boston, MA, USA.
authors.forename: Kendra N
authors.initials: KN
authors.lastname: Iskander
authors.forename: Florin L
authors.initials: FL
authors.lastname: Craciun
authors.forename: David M
authors.initials: DM
authors.lastname: Stepien
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Duffy
authors.forename: Jiyoun
authors.initials: J
authors.lastname: Kim
authors.forename: Rituparna
authors.initials: R
authors.lastname: Moitra
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Vaickus
authors.forename: Marcin F
authors.initials: MF
authors.lastname: Osuchowski
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Remick
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology*; D000818:Animals; D002423:Cause of Death; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000097:blood; D008026:Ligation; D051379:Mice; D011677:Punctures; D012128:Respiratory Distress Syndrome / Q000473:pathology*; D018805:Sepsis / Q000401:mortality* / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D015850:Interleukin-6