Endocannabinergic Modulation of Interleukin-1β in Mouse Hippocampus under Basal Conditions and after in vivo Systemic Lipopolysaccharide Stimulation

Objective: Cannabinoids play an important role in the suppression of proinflammatory cytokine production in the periphery and brain. In this study, we explored whether endogenous activation of cannabinoid (CB) 1 receptors (CB1Rs) affects interleukin (IL)-1 beta levels in the mouse hippocampus under basal conditions and following stimulation with in vivo bacterial lipopolysaccharide (LPS, 250 mu g/kg i.p.). Methods:IL-1 beta levels were determined in the hippocampi of wildtype (WT), CB1R-/- and P2X(7) receptor (P2X(7)R)-/- mice using an ELISA kit. Results: Basal but not LPS-induced IL-1 beta levels were downregulated when CB1R function was abrogated by genetic deletion, suggesting that endocannabinoids contributed to basal IL-1 beta content in the mouse hippocampus. AM251 (3 mg/kg i.p.), an antagonist of CB1Rs, also inhibited basal IL-1 beta protein in WT but not in CB1R-/- mice. In the absence of P2X(7)R, LPS-induced IL-1 beta production was lower, while the inhibitory effect of CB1R antagonists on basal IL-1 beta was significantly attenuated. The LPS-induced elevation in IL-1 beta production was decreased in the presence of AM251 and AM281, with no significant difference between WT and P2X(7)R-/- mice. Conclusions: CB1Rs are responsible for the modulation of basal IL-1 beta levels in the hippocampus, while the effects of CB1 antagonists on systemic LPS-induced IL-1 beta concentrations are independent of CB1Rs. Copyright (C) 2011 S. Karger AG, Basel