Cecum ligation and dissection: a novel modified mouse sepsis model
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Updated: May 15, 2026
Cecal Ligation Puncture Procedure
Published on: May 7, 2011
Haitham Mutlak1, Carla Jennewein, Nguyen Tran
1Clinic of Anesthesiology, Intensive Care Medicine and Pain Therapy, Goethe-University Hospital Frankfurt, Frankfurt am Main, Germany.
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.
Materials And 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.
Insights
A new mouse model of sepsis, cecum ligation and dissection (CLD), accurately mimics human clinical conditions. This improved sepsis model shows reliable organ inflammation and liver damage, aiding sepsis research.
Area of Science:
- Translational Medicine
- Sepsis Pathophysiology
- Animal Models
Background:
- High failure rate of sepsis therapeutics in human translation necessitates improved preclinical models.
- Existing sepsis models do not accurately simulate clinical scenarios, hindering therapeutic development.
- A novel, clinically relevant mouse model is crucial for advancing sepsis research.
Purpose of the Study:
- To develop and validate a modified mouse model of sepsis that more accurately reflects human clinical conditions.
- To compare the novel model's efficacy in simulating sepsis-induced organ damage and inflammation against the classic cecum ligation and puncture (CLP) model.
Main Methods:
- Sepsis induced in C57Bl/6 mice using cecum ligation and dissection (CLD) followed by relaparotomy and peritoneal lavage.
- Assessment of lung impairment via neutrophil invasion and measurement of proinflammatory cytokines (IL-6, MCP-1) using RT-PCR and Luminex.
- Evaluation of liver damage through aspartate transaminase (AST) and alanine transaminase (ALT) measurements, compared to sham and CLP groups.
Main Results:
- The CLD model demonstrated significantly increased lung IL-6 and MCP-1 mRNA levels and neutrophil invasion.
- CLD induced significant upregulation of hepatic IL-6, TNF-α, IL-10, and MCP-1, alongside elevated ALT levels.
- Systemic inflammation markers (IL-6, TNF-α, IL-1β, IL-10, MCP-1) were significantly higher in CLD animals compared to sham and CLP groups.
Conclusions:
- The modified CLD model reliably induces organ inflammation and liver damage, closely mimicking clinical sepsis.
- This enhanced sepsis model exhibits mortality rates comparable to clinical settings, offering a more accurate research platform.
- The CLD model provides a reliable onset of sepsis, improving the translational validity of preclinical sepsis studies.
