Lidocaine Enhances Apoptosis and Suppresses Mitochondrial Functions of Human Neutrophil In Vitro

Abstract

Neutrophils play an essential role in innate immunity and against infection. Mitochondria are organelles that produce energy in the form of adenosine triphosphate (ATP), which is required for maintaining the function and structure of cells and organs. Although local anesthetics (LAs) are widely used in clinical practice, it remains unclear whether LAs such as lidocaine, ropivacaine, and bupivacaine affect neutrophil mitochondrial functions. The aim of this study was to examine whether LAs have any effects on human neutrophil mitochondrial functions. Freshly isolated human neutrophils were incubated with lidocaine, ropivacaine, or bupivacaine. The oxidative burst and phagocytic activity of neutrophils and apoptotic rate of neutrophils were measured to assess the effect of LAs on neutrophil functions. The ATP concentration, mitochondrial transmembrane potential (Deltapsim), and neutrophil mitochondrial morphology were also measured to evaluate the effect of LAs on mitochondrial functions. Lidocaine (400 microm) induced a reduction in the oxidative burst and phagocytosis activity of neutrophils by approximately 20%. The ATP concentration was significantly lower in lidocain-treated neutrophils compared with control neutrophils (876 +/- 25 vs. 1,332 +/- 76 pmol/10(6) neutrophils; p < 0.05). Mitochondrial transmembrane potential (Deltapsim) was also significantly lower in lidocaine-treated neutrophils compared with control neutrophils (p < 0.05). Lidocaine also induced mitochondrial structural changes and induced apoptosis of neutrophils. Ropivacaine and bupivacaine had no effect on neutrophil functions including mitochondrial function. Furthermore, the study of mitochondrial function depletion demonstrated that neutrophil function requires active mitochondrial function. Although ropivacaine and bupivacaine had no effect on neutrophil and mitochondrial functions, lidocaine suppressed neutrophil function, inhibited ATP synthesis, reduced mitochondrial membrane potential, and induced apoptosis.