Azuma Yasutaka, Ohura Kiyoshi
Department of Pharmacology, Osaka Dental University, Hirakata, Osaka 573-1121, Japan.
Curr Drug Targets Immune Endocr Metabol Disord. 2004 Mar;4(1):29-36. doi: 10.2174/1568008043339974.
There is accumulating evidence that local anesthetics have immunological properties in addition to their direct anesthetic activity. Because local anesthetics are often used together with blood vessel contraction drugs, such as epinephrine and felypressin in the clinical setting, we have examined possible abilities of both local anesthetic alone including lidocaine, mepivacaine, procaine, prilocaine and tetracaine, and local anesthetics with blood vessel contraction drugs including lidocaine with epinephrine and prilocaine with felypressin on the functions related to natural immunity in neutrophils and macrophages. In contrast, lidocaine, mepivacaine, procaine, prilocaine and tetracaine all inhibited adhesion, chemotaxis, phagocytosis, and the production of superoxide anion and hydrogen peroxide by neutrophils and macrophages. Lidocaine with epinephrine and prilocaine with felypressin were effective in significantly inhibiting adhesion, chemotaxis, phagocytosis, and the production of hydrogen peroxide by neutrophils and macrophages. Interestingly, lidocaine with epinephrine potentiated the production of superoxide anion, whereas prilocaine with felypressine inhibited the production, irrespective of cells. In addition, epinephrine potentiated the production of superoxide anion, whereas epinephrine inhibited the production of hydrogen peroxide as well as lidocaine with epinephrine. This potentiation by epinephrine was not prevented by adrenergic antagonists. Furthermore, superoxide dismutase potentiated the production of hydrogen peroxide, which was in part prevented by epinephrine. These results suggest that local anesthetics may inhibit the functions related to natural immunity in neutrophils and macrophages. In addition, lidocaine with epinephrine evidently differs from prilocaine with felypressine regarding the molecular mechanisms underlying the modulation of superoxide anion production by neutrophils and macrophages.
越来越多的证据表明，局部麻醉药除了具有直接麻醉活性外，还具有免疫特性。由于在临床环境中局部麻醉药常与血管收缩药物如肾上腺素和去氧肾上腺素一起使用，我们研究了单独的局部麻醉药（包括利多卡因、甲哌卡因、普鲁卡因、丙胺卡因和丁卡因）以及与血管收缩药物联合使用的局部麻醉药（包括利多卡因加肾上腺素和丙胺卡因加去氧肾上腺素）对中性粒细胞和巨噬细胞中与天然免疫相关功能的潜在影响。相比之下，利多卡因、甲哌卡因、普鲁卡因、丙胺卡因和丁卡因均抑制中性粒细胞和巨噬细胞的黏附、趋化、吞噬以及超氧阴离子和过氧化氢的产生。利多卡因加肾上腺素和丙胺卡因加去氧肾上腺素能有效显著抑制中性粒细胞和巨噬细胞的黏附、趋化、吞噬以及过氧化氢的产生。有趣的是，利多卡因加肾上腺素增强了超氧阴离子的产生，而丙胺卡因加去氧肾上腺素则抑制了超氧阴离子的产生，与细胞类型无关。此外，肾上腺素增强了超氧阴离子的产生，而肾上腺素与利多卡因加肾上腺素一样抑制了过氧化氢的产生。肾上腺素的这种增强作用不受肾上腺素能拮抗剂的阻止。此外，超氧化物歧化酶增强了过氧化氢的产生，而肾上腺素部分阻止了这种增强作用。这些结果表明，局部麻醉药可能抑制中性粒细胞和巨噬细胞中与天然免疫相关的功能。此外，利多卡因加肾上腺素与丙胺卡因加去氧肾上腺素在中性粒细胞和巨噬细胞中超氧阴离子产生调节的分子机制方面明显不同。
