Inhibitory effects of amide local anaesthetics on stimulus-induced human leukocyte metabolic activation, LTB4 release and IL-1 secretion in vitro.
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 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 LTB4 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, LTB4 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.
Department of Anaesthesiology, Central Hospital, Mölndal, Sweden.
R
R
Sinclair
A S
AS
Eriksson
C
C
Gretzer
J
J
Cassuto
P
P
Thomsen
D000936:Antigen-Antibody Complex; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006098:Granulocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008163:Luminescent Measurements; D008165:Luminol; D015054:Zymosan / Q000494:pharmacology
D000936:Antigen-Antibody Complex; D007375:Interleukin-1; D007975:Leukotriene B4; D008165:Luminol; D015054:Zymosan; D008012:Lidocaine; D002045:Bupivacaine