Propofol’s anti-inflammatory action is independent of endocannabinoid system activation in microglia

Propofol is well-known for its inhibitory effects in the central nervous system (CNS) as an intravenous anesthetic. Less is known about propofol’s impact on microglial activity. Studies have suggested a link to the endocannabinoid system (ECS). Propofol has been shown to indirectly modulate cannabinoid type 1 (CB1R) and type 2 (CB2R) receptors on microglia, with CB2R playing a key role in regulating anti-inflammatory immune responses. The objective of this study was to evaluate potential anti-inflammatory effects of propofol on microglia and to determine whether any observed effects are associated with the ECS. To investigate this, we treated LPS-stimulated SIM-A9 mouse-derived microglial cells with propofol, both in the presence and absence of antagonists for CB2R and CB1R, and assessed the cell viability and the production of the cytokines TNF and IL-6. The results demonstrated that cell viability was stable at propofol concentrations of 20, 40, and 80 µM. Production of TNF and IL-6 was reduced significantly upon propofol treatment. This effect of cytokine production did not change following administration of CB1R and/or CB2R antagonists. In conclusion, the results demonstrated that propofol exhibits anti-inflammatory effects, which do not appear to be mediated through ECS activation.