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Updated: May 24, 2026

Colon Ascendens Stent Peritonitis (CASP) - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Cannabinoid receptor 2 activation reduces intestinal leukocyte recruitment and systemic inflammatory mediator release
Christian Lehmann1, Mandana Kianian, Juan Zhou
1Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 2Y9. chlehmann@dal.ca
Introduction:
Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models.
Methods:
In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed.
Results:
HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals.
Conclusion:
CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
Insights
Activating cannabinoid receptor 2 (CB2R) reduces leukocyte activation and inflammatory mediators in sepsis models. Targeting the CB2R pathway shows therapeutic potential for sepsis treatment.
Area of Science:
- Immunology
- Pharmacology
- Critical Care Medicine
Background:
- Cannabinoid receptor 2 (CB2R) expression increases during sepsis.
- The role of CB2R modulation in sepsis hyperinflammation is unclear.
- This study investigates CB2R's effect on leukocyte activation in experimental sepsis.
Purpose of the Study:
- To examine the impact of CB2R manipulation on leukocyte activation in the intestinal microcirculation.
- To evaluate CB2R agonists and antagonists in endotoxemia and peritonitis sepsis models.
Main Methods:
- Two acute experimental sepsis models were used: lipopolysaccharide (LPS)-induced endotoxemia and colon ascendens stent peritonitis (CASP).
- Rats were treated with CB2R agonist HU308 or antagonist AM630.
- Intravital microscopy, hemodynamic monitoring, histology, and inflammatory mediator measurements were performed.
Main Results:
- CB2R agonist HU308 significantly decreased leukocyte adhesion in both sepsis models.
- High-dose HU308 (10 mg/kg) treatment in CASP animals reduced systemic inflammatory mediators.
Conclusions:
- CB2R activation effectively reduces leukocyte activation and inflammatory mediator release in acute experimental sepsis.
- Targeting the CB2R pathway presents a potential therapeutic strategy for sepsis.
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