Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila

Delta-9-tetrahydrocannabinol (THC) injection suppresses serum interleukin-12 (IL-12) levels in Legionella pneumophila-infected mice. Dendritic cells are a major producer of IL-12 and mouse, bone marrow-derived dendritic cell cultures produced high levels of the IL-12p40 following L. pneumophila infection. Treatment with THC suppressed this cytokine response in a concentration-dependent manner and the endocannabinoid, 2-arachidonoyolglycerol, less potently suppressed cytokine production. Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB1), cannabinoid CB2 receptor, and vanilloid receptor 1 (TRPV1) and the addition of the Gi inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 μM THC but not by 10 μM THC. Furthermore, THC suppression was partially attenuated in dendritic cells from cannabinoid CB1 receptor and CB2 receptor knockout mice and in dendritic cells co-treated with THC and cannabinoid receptor antagonists. Cytokine suppression was not attenuated by pretreatment with the TRPV1 antagonist, capsazepine. These results suggest that THC-induced suppression of serum IL-12 is partly due to a suppression of IL-12 production by dendritic cells and that Gi signaling and cannabinoid receptors, but not TRPV1, are involved in this suppressive effect.