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

Abstract

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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