Guineensine increases the production of pro-inflammatory cytokines in activated M1 macrophages and shows inhibitory effects on resting and M2 macrophages

Guineensine, a natural compound isolated from several species of pepper plants, is an inhibitor of endocannabinoid uptake and probably an indirect CB1 receptor (CB1R) agonist. As an inhibitor of cellular uptake of AEA and 2-AG, guineensine has been shown to exhibit cannabimimetic effects; however, the role of this compound in the control of inflammation and macrophage activation is not yet clear. Here we used the human macrophages-like THP-1 cell line to study guineensine. When stimulated with lipopolysaccharide (LPS) and IFN-γ, guineensine increases production of IL-1β, TNF-α, and monocyte chemoattractant protein (MCP)-1 (the latter two up to 2.5-fold). Interestingly, when resting macrophage-like or macrophage-like stimulated with IL- 4 and IL-13 (M2) were exposed to guineensine, MCP-1 and IL-8 levels were significantly decreased. No significant differences between phagocytosis and respiratory burst (ROS production) in activated macrophages treated with guineensine were found. These results suggest a differential outcome between M1, M2 and resting macrophages-like and immune response when exposed to guineensine.