Lidocaine attenuates lipopolysaccharide-induced inflammatory responses and protects against endotoxemia in mice by suppressing HIF1α-induced glycolysis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infections. Previous studies have indicated that lidocaine, an amide local anesthetic, has anti-inflammatory properties; however, the underlying mechanism remains unclear. In this study, we have shown that lidocaine dose-dependently inhibits lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in macrophages and that lidocaine protects mice from LPS-induced inflammation. Moreover, we have demonstrated that lidocaine reduces the release of TNF-α and IL-6 through the reduction of the expression of GLUT1 and HK2 to further suppress HIF1α-induced aggravation of inflammatory cascades. Lidocaine can inhibit the enhanced glycolysis and glycolytic capacity induced by LPS in the macrophages. As an inhibitor of PHDs (prolyl hydroxylases), Dimethyloxalylglycine (DMOG) can reduce the anti-inflammatory effects of lidocaine. In conclusion, the present study indicates that lidocaine can be used as a potential therapeutic agent for sepsis.