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Inhibitory effects of amide local anaesthetics on stimulus‐induced human leukocyte metabolic activation, LTB 4 release and IL‐1 secretion in vitro
Author(s) -
Sinclair R.,
Eriksson A. S.,
Gretzer C.,
Cassuto J.,
Thomsen P.
Publication year - 1993
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1993.tb03693.x
Subject(s) - zymosan , leukotriene b4 , lipopolysaccharide , medicine , pharmacology , lidocaine , bupivacaine , bovine serum albumin , in vitro , radioimmunoassay , in vivo , stimulation , immunology , chemistry , inflammation , endocrinology , biochemistry , anesthesia , biology , microbiology and biotechnology
The anti‐inflammatory effects of the amide local anaesthetics lidocaine and bupivacaine were evaluated in vitro by 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 B 4 (LTB 4 ) and interleukin‐1 (IL‐1) evaluated by radioimmunoassay (RIA). Pretreatment of suspended PMNGs and monocytes with the anaesthetics caused a marked inhibition of LTB 4 release 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, LTB 4 and 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 described in vivo.