ABSTRACT: ABSTRACT: INTRODUCTION: Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyper-inflammatory phase of the disease. Therefore, the aim of this study was to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. METHODS: 1.) Endotoxemia model: We studied 4 groups of Lewis rats: controls (CON), LPS (lipopolysaccharide), LPS + CB2R agonist (HU308, 2.5 mg/kg), and LPS + CB2R antagonist (AM630, 2.5 mg/kg). 2.) Colon ascendens stent peritonitis (CASP)-induced sepsis model: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy (IVM) was performed two 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. CONCLUSIONS: 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.
Critical care (London, England) 03/2012; 16(2):R47. · 4.61 Impact Factor