Delayed Treatment with Lidocaine Reduces Mouse Microglial Cell Injury and Cytokine Production After Stimulation with Lipopolysaccharide and Interferon γ

Abstract

Neuroinflammation is an important pathological process for almost all acquired neurological diseases. Microglial cells play a critical role in neuroinflammation. We determined whether lidocaine, a local anesthetic with anti-inflammatory property, protected microglial cells and attenuated cytokine production from activated microglial cells. Mouse microglial cultures were incubated with or without 1 μg/mL lipopolysaccharide and 10 U/mL interferon γ (IFNγ) for 24 hours in the presence or absence of lidocaine for 1 hour started at 2, 3, or 4 hours after the onset of lipopolysaccharide and IFNγ stimulation. Lactate dehydrogenase release and cytokine production were determined after the cells were stimulated by lipopolysaccharide and IFNγ for 24 hours. Lidocaine dose-dependently reduced lipopolysaccharide and IFNγ-induced microglial cell injury as measured by lactate dehydrogenase release. This effect was apparent with lidocaine at 2 μg/mL (30.3% ± 5.8% and 23.1% ± 9.7%, respectively, for stimulation alone and the stimulation in the presence of lidocaine, n = 18, P = 0.025). Lidocaine applied at 2, 3, or 4 hours after the onset of lipopolysaccharide and IFNγ stimulation reduced the cell injury. This lidocaine effect was not affected by the mitochondrial K(ATP) channel inhibitor 5-hydroxydecanoate. Similar to lidocaine, QX314, a permanently charged lidocaine analog that usually does not permeate through the plasma membrane, reduced lipopolysaccharide and IFNγ-induced microglial cell injury. QX314 also attenuated the stimulation-induced interleukin-1β production. Delayed treatment with lidocaine protects microglial cells and reduces cytokine production from these cells. These effects may involve action site(s) on the cell surface.