Local anesthetic effects on human neutrophil priming and activation.
BACKGROUND
The anti-inflammatory effects of local anesthetics (LAs) are well documented. Local anesthetics in micromolar concentrations inhibit extracellular oxygen release in isolated neutrophils; the underlying mechanism seems to be an inhibition of leukocyte priming. It remains unclear, however, if first, these effects also can be observed in whole blood, and second, if the priming of other neutrophil functions is similarly attenuated by LAs. Furthermore, the effects of LAs on intracellular generation of oxidative species remain to be investigated.


METHODS
Whole-blood samples from healthy volunteers were incubated for 0, 1, or 3 hrs with different concentrations (10 to 10 M) of either lidocaine, ropivacaine, QX314, or NaCl 0.9% as control. Dihydroethidium was added to quantify oxidative burst. Samples were primed with platelet-activating factor (PAF, 10 M) and/or activated with formyl-methyl-leucyl-phenylalanine (10 M) for 15 mins each. After staining for CD11b and lysis of erythrocytes, samples were analyzed by flow cytometry.


RESULTS
Priming of leukocytes is a relevant mechanism in whole blood. Platelet-activating factor stimulates the priming of oxidative burst and CD11b expression. Lidocaine up to millimolar concentrations did not affect the PAF priming and formyl-methyl-leucyl-phenylalanine activation of oxidative burst. The priming of CD11b expression and the priming and activation of changes in cell morphology were significantly attenuated by lidocaine.


CONCLUSIONS
The intracellular generation of reactive oxygen species remains largely unaffected by LAs in clinical concentrations. This suggests that the anti-inflammatory effects of LAs do not interfere with the host defense.
Ploppa
Annette
A
Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls University, Tuebingen, Germany. annette.ploppa@uni-tuebingen.de
Kiefer
Ralph-Thomas
RT
Haverstick
Doris M
DM
Groves
Danja S
DS
Unertl
Klaus E
KE
Durieux
Marcel E
ME
D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000097:blood / Q000494:pharmacology*; D039481:CD11b Antigen / Q000097:blood; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010972:Platelet Activating Factor / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D000077212:Ropivacaine
D000577:Amides; D000779:Anesthetics, Local; D039481:CD11b Antigen; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; C012647:QX-314; D000077212:Ropivacaine; D008012:Lidocaine