International Journal of Immunopharmacology
Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils
Introduction
Neutrophils are often the first cells of the immune system to encounter invaders, such as bacteria and fungi. The neutrophil response to infection in vivo is initiated by adherence of neutrophils to vascular endothelial cells, and progresses to the directed migration of neutrophils into the extravascular tissue space. The migration of neutrophils culminates in neutrophil-mediated phagocytosis and intracellular killing of the invading microorganisms by generation of bactericidal reactive oxygen species derived from the superoxide anion radical.
There is accumulating evidence that local anesthetics have immunological properties other than direct anesthetic activity. These include interactions with, and alterations in functions of host phagocytes. For instance, lidocaine was found to inhibit neutrophil functions such as chemotaxis [1], [2], phagocytosis [2], [3], and lysosomal enzyme release and superoxide anion production [1], [4]. Our previous studies gave support to the notion that lidocaine disrupts macrophage functions [5], [6]. These subjects are important, given that phagocytes are essential for controlling almost all infections and are mediators of inflammation. In this article, therefore, we have simultaneously examined the comparison of effects of other local anesthetics including lidocaine on adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide of rat peripheral neutrophils.
Section snippets
Materials
Fluorescein conjugated Escherichia coli (K-12) bioparticles were purchased from Molecular Probes (Eugene, OA). Lidocaine, Mepivacaine, and Prilocaine were supplied by Fujisawa Pharmaceuticals (Osaka, Japan). Procaine was obtained from Daiichi Pharmaceuticals (Tokyo, Japan). Tetracaine was provided by Kyorin Pharmaceuticals (Tokyo, Japan). Other chemicals used were all of the highest purity commercially available.
Isolation of neutrophils from peritoneum
The protocol employed here meets the guidelines of the Japanese Society for
Viability and adhesion
Trypan blue exclusion test showed blue staining (nonviable) of less than 5% of neutrophils incubated with all of local anesthetics examined at 1 mg/ml (data not shown). The addition of local anesthetics at a dose of 1 mg/ml significantly inhibited the adhesion of neutrophils (Fig. 1). Among the local anesthetics tested, tetracaine induced the most potent inhibition of adhesion. Less potent inhibition was found for lidocaine, mepivacaine, procaine, and for prilocaine. However, no marked changes
Discussion
The essential importance of the findings presented in this study is that local anesthetics other than lidocaine affect neutrophil function. Since concentration of local anesthetics used in clinical anesthesia is 20 mg/ml, local anesthetics at 0.1 mg/ml occur in peripheral tissue, but not in plasma concentration. The local anesthetics at a therapeutic concentration examined in this study inhibited neutrophil functions including the production of superoxide anion and hydrogen peroxide, but not
Acknowledgements
This work was performed in part at the Institute of Dental Research, Osaka Dental University.
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