Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB4release and IL‐1 secretionin vitro

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Abstract
The anti‐inflammatory effects of the amide local anaesthetics lidocaine and bupivacaine were evaluatedin vitroby examination of the metabolic activation and secretory responses of human polymorphonuclear granulocytes (PMNGs) and mononuclear cells. Pretreatment with lidocaine or bupivacaine had a dose‐dependent inhibitory effect on PMNG luminol‐amplified chemiluminescence stimulated by bovine serum albumin (BSA)/anti‐BSA immune complexes (IC) or by serum‐opsonized zymosan (SOZ) particles. Both lidocaine and bupivacaine inhibited the release of the inflammatory mediators leukotriene B4(LTB4) and interleukin‐1 (IL‐1) evaluated by radioimmunoassay (RIA). Pretreatment of suspended PMNGs and monocytes with the anaesthetics caused a marked inhibition of LTB4release when the cells were stimulated with SOZ. In short‐term (24 h) cultures of mononuclear cells the addition of lidocaine or bupivacaine reduced, in a dose‐dependent manner, the level of IL‐1 detected after stimulation with lipopolysaccharide (LPS). In all three assays (chemiluminescence, LTB4and IL‐1 RIA) bupivacaine was found to be more potent than lidocaine. The present results show that amide local anaesthetics have marked suppressive effects on the metabolic activation and secretory functions of leukocytes stimulated by different agonists. Although the detailed mechanisms for these effects are not known, they may explain part of the potent anti‐inflammatory actions of local anaesthetics previously describedin vivo.