Comparison of inhibitory effects of local anesthetics on immune functions of neutrophils

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Abstract

Immunological effects of a variety of local anesthetics on adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils were compared. Neutrophils were isolated by peritoneal lavage from rats, 4 h after injection of 1% glycogen. Lidocaine, mepivacaine, procaine, prilocaine and tetracaine at 1 mg/ml inhibited adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide in neutrophils. Moreover, lidocaine, mepivacaine, procaine and prilocaine at 0.1 mg/ml inhibited the production of superoxide anion and hydrogen peroxide but not adhesion or phagocytosis. In contrast, tetracaine at 0.1 mg/ml inhibited phagocytosis, and the production of superoxide anion and hydrogen peroxide but not adhesion. At 0.01 mg/ml, however, tetracaine inhibited the production of superoxide anion and hydrogen peroxide; in contrast, other drugs failed to affect neutrophil function. These results suggest that the local anesthetics may affect adhesion, phagocytosis, and the production of superoxide anion and hydrogen peroxide by 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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