Cecum ligation and dissection: a novel modified mouse sepsis model

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.