title: Cecum ligation and dissection: a novel modified mouse sepsis model.
abstract: BACKGROUND
  The fact that many sepsis therapeutics failed to be translated into the human indicates that there is still a serious need to reassess our models of sepsis research. We aimed to develop a novel modified model of sepsis in the mouse, which simulates the clinical situation more accurately.
  
  
  METHODS
  Sepsis was induced in C57Bl/6 mice by dissecting the cecum and placing the discontinued organ back into the abdomen (cecum ligation and dissection [CLD]). Septic animals were relaparotomized after 6 h, followed by peritoneal lavage, and antibiotic treatment. Results were compared with shams or the classic colon ligation and puncture (CLP) model. The postoperative lung impairment was assessed using neutrophil invasion as a surrogate. Proinflammatory cytokines were measured by either real-time polymerase chain reaction or Luminex technology, and liver damage was evaluated by aspartate transaminase and alanine transaminase measurements.
  
  
  RESULTS
  In CLD animals with relaparotomy after 6 h, lung interleukin (IL) 6, monocyte chemoattractant protein (MCP)-1 messenger RNA levels, and neutrophil invasion were significantly increased. Liver messenger RNA expression in CLD animals was significantly upregulated for IL-6, tumor necrosis factor alpha, IL-10, and MCP-1 compared with sham and CLP animals. Significantly higher levels of alanine transaminase were observed in CLD animals. Finally, systemic inflammation as measured by plasma IL-6, tumor necrosis factor alpha, IL-1β, IL-10, and MCP-1 was significantly increased in all CLD animals compared with shams, whereas CLP animals only showed an insignificant increase in the latter molecules.
  
  
  CONCLUSIONS
  Our modifications to the classic CLP model significantly produced organ inflammation, liver damage, and a similar mortality compared with a clinical setting, with a reliable onset of sepsis.
authors.affiliation: Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
authors.forename: Haitham
authors.initials: H
authors.lastname: Mutlak
authors.forename: Carla
authors.initials: C
authors.lastname: Jennewein
authors.forename: Nguyen
authors.initials: N
authors.lastname: Tran
authors.forename: Martina
authors.initials: M
authors.lastname: Mehring
authors.forename: Kathrina
authors.initials: K
authors.lastname: Latsch
authors.forename: Katharina
authors.initials: K
authors.lastname: Habeck
authors.forename: Pia Alexandra
authors.initials: PA
authors.lastname: Ockelmann
authors.forename: Bertram
authors.initials: B
authors.lastname: Scheller
authors.forename: Kai
authors.initials: K
authors.lastname: Zacharowski
authors.forename: Patrick
authors.initials: P
authors.lastname: Paulus
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002432:Cecum / Q000601:surgery*; D004195:Disease Models, Animal; D004210:Dissection; D006505:Hepatitis / Q000209:etiology; D007813:Laparotomy; D008026:Ligation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000209:etiology; D018805:Sepsis / Q000209:etiology*
chemical_list: D000900:Anti-Bacterial Agents