CB2 Cannabinoid Receptors Contribute to Bacterial Invasion and Mortality in Polymicrobial Sepsis

Balázs Csóka, Department Of Surgery, University Of Medicine, Dentistry Of New Jersey-New Jersey Medical School, Newark, New Jersey, United States Of America, Zoltán H. Németh, Morristown Memorial Hospital, Morristown

Endocannabinoids that are produced excessively in sepsis are potential factors leading to immune dysfunction, because they suppress immune cell function by binding to G-protein-coupled CB 2 receptors on immune cells. As shows, the levels of IκBα were increased in the spleen of CB 2 KO as compared to WT mice, indicating decreased NF-κB activation in KO mice. We then determined the levels of macrophage-inflammatory protein-2 (MIP-2), a crucial chemokine that mediates inflammatory responses, in the plasma and peritoneal lavage fluid of CB 2 KO and WT mice subjected to CLP, and we found that CLP-induced concentrations of MIP-2 were diminished in CB 2 KO mice as compared with their WT counterparts when measured at 16 h after CLP ( ). To begin to study the role of CB 2 receptors, we first investigated the effect of CB 2 deficiency in CLP-induced septic peritonitis by monitoring the survival of CB 2 WT and KO mice. Using the CLP model of sepsis, we found that CB 2 receptor activation by endogenously released cannabinoids contributes to mortality, bacterial invasion, IL-10 production, and immune cell death in sepsis.

Visit Link