Inhibition of GPR 55 improves dysregulated immune response in experimental sepsis.

Sepsis is a medical condition caused by dysregulated systemic inflammatory response against infection, resulting in high mortality. Despite intensive research over the last few decades, the results from multiple clinical trials targeting specific inflammatory mediators have been disappointing. In the present study, we investigated the role of G protein-coupled receptor GPR55 modulation on immune response in an experimental sepsis model (endotoxemia). Immune response was evaluated by analyzing leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation using intravital microscopy. In addition, the levels of plasma inflammatory cytokines were measured. The results demonstrated that GPR55 inhibition using antagonists, CID16020046 or O-1918, significantly reduced leukocyte adherence in intestinal submucosal venules and decreased proinflammatory cytokine TNF-α and IL-6 production. These data suggest that GPR55 inhibition may be a novel therapeutic target for attenuating hyperinflammation during sepsis.