Leukocyte function can be modulated through the cannabinoid receptor 2 (CB2R). Using a cecal ligation and puncture (CLP)
model of sepsis, we examined the role of the CB2R during the immune response to an overwhelming infection. CB2R-knock out
(KO) mice showed decreased survival as compared with wild-type mice. CB2R-KO mice also had increased serum IL-6 and
bacteremia. Twenty-four hours after CLP, the CB2R-deficient mice had increased lung injury. Additionally, CB2R-deficiency led
to increased neutrophil recruitment, decreased neutrophil activation, and decreased p38 activity at the site of infection. Consistent
with a novel role for CB2R in sepsis, CB2R-agonist treatment in wild-type mice increased the mean survival time in response to
CLP. Treatment with CB2R-agonist also decreased serum IL-6 levels, bacteremia, and damage to the lungs compared with
vehicle-treated mice. Finally, the CB2R agonist decreased neutrophil recruitment, while increasing neutrophil activation and p38
activity at the site of infection compared with vehicle-treated mice. These data suggest that CB2R is a critical regulator of the
immune response to sepsis and may be a novel therapeutic target.
