• Christian Lehmann, Mandana Kianian, Juan Zhou, Inga Küster, Rieke Kuschnereit, Sara Whynot, Orlando Hung, Romesh Shukla, Brent Johnston, Vladimir Cerny, Dragan Pavlovic, Alexander Spassov, and Melanie Em Kelly.
• Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 2Y9. chlehmann@dal.ca
• Crit Care. 2012 Jan 1; 16 (2): R47.

IntroductionCannabinoid 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.MethodsIn 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.ResultsHU308 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.ConclusionCB2R 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.

21 keywords...

hide…