Hae-Jeong Jeong1, Daowei Lin, Liaoliao Li, Zhiyi Zuo. 1. Department of Anesthesiology, University of Virginia, 1 Hospital Drive, PO Box 800710, Charlottesville, VA 22908-0710, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: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. RESULTS: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. CONCLUSIONS: 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.
Authors: Gildasio S De Oliveira; Kenyon Duncan; Paul Fitzgerald; Antoun Nader; Robert W Gould; Robert J McCarthy Journal: Obes Surg Date: 2014-02 Impact factor: 4.129