Local anesthetics time-dependently inhibit staphylococcus aureus phagocytosis, oxidative burst and CD11b expression by human neutrophils.
OBJECTIVE
Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S. aureus, oxidative burst, and CD11b expression by human neutrophils. To test this hypothesis, we reanalyzed data from a previous study.


METHODS
Blood samples from 11 healthy volunteers were incubated with lidocaine (1,846 mumol/L), bupivacaine (770 mumol/L) or ropivacaine (801 mumol/L) for 30 minutes. Thereafter, bacteria were added, either fluorescently labeled for determination of phagocytosis, or unstained for determination of oxidative burst and CD11b expression. After an additional incubation for 0, 10, 30, or 60 minutes, phagocytosis was stopped and neutrophils were stained with monoclonal antibodies for flow cytometric analysis. Data were analyzed by analysis of variance for repeated measurements.


RESULTS
Lidocaine and bupivacaine inhibited neutrophil functions in a time-dependent manner (P < .05). Prolonged local anesthetic exposure reduced the fraction of ingesting neutrophils by 20% +/- 12% (mean +/- SD) and 7% +/- 7%, bacterial uptake by 19% +/- 16% and 14% +/- 12%, oxidative burst by 29% +/- 23% and 28% +/- 25%, and CD11b expression by 66% +/- 24% and 25% +/- 21% for lidocaine and bupivacaine, respectively. Ropivacaine exerted a time-dependent effect on CD11b expression only (24% +/- 34%; P < .05).


CONCLUSIONS
Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted.
Ploppa
Annette
A
Department of Anesthesiology and Intensive Care Medicine, Eberhard-Karls University Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. annette.ploppa@uni-tuebingen.de
Kiefer
Ralph-Thomas
RT
Krueger
Wolfgang A
WA
Unertl
Klaus E
KE
Durieux
Marcel E
ME
D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D039481:CD11b Antigen / Q000032:analysis*; D002448:Cell Adhesion / Q000187:drug effects; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects*; D016897:Respiratory Burst / Q000187:drug effects*; D000077212:Ropivacaine; D013211:Staphylococcus aureus / Q000276:immunology*; D013997:Time Factors
D000577:Amides; D000779:Anesthetics, Local; D039481:CD11b Antigen; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine