Lipid solubility- and concentration-dependent attenuation of in vitro natural killer cell cytotoxicity by local anesthetics.
BACKGROUND
Natural killer (NK) cells constitute an essential component of the innate immune system in the defence against infected and malignant cells. In this study the in vitro effect on NK cell activity of three different local anesthetics with different lipid solubility was investigated.


METHODS
Venous blood from seven healthy volunteers was incubated with three amide local anesthetics with three different concentrations of lipid solubility: lidocaine 0.50, 1.00 and 2.00 mg/ml, ropivacaine 0.375, 0.75 and 1.50 mg/ml, and bupivacaine 0.25, 0.50 and 1.00 mg/ml. After 1 h of incubation, mononuclear cells were isolated and cryopreserved until tested for NK cell cytotoxicity in a 4-h 51Cr-release assay against K-562 target cells. Natural killer cell cytotoxicity of mononuclear cells incubated with isotonic saline was used as the control.


RESULTS
A significant suppression in NK cell cytotoxicity was demonstrated for all three local anesthetic agents when the NK cell cytotoxicity was compared with the cytotoxicity estimated after incubation with the isotonic saline (P<0.004). Moreover a significant lipid solubility-dependent effect (P=0.0001) as well as an overall concentration-dependent effect (P<0.0001) on the NK cell cytotoxicity was found.


CONCLUSIONS
The results of the present in vitro study suggest a negative association between the estimated NK cell cytotoxicity and the lipid solubility as well as the concentrations of the three local anesthetic agents tested.
Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Institute of Medical Microbiology and Immunology, The Bartholin Building, Denmark. krog@akhphd.au.dk
J
J
Krog
M
M
Hokland
P
P
Ahlburg
E
E
Parner
E
E
Tønnesen
D000328:Adult; D000577:Amides / Q000494:pharmacology; D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology*; D002045:Bupivacaine / Q000494:pharmacology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008012:Lidocaine / Q000494:pharmacology; D008055:Lipids; D015999:Multivariate Analysis; D000077212:Ropivacaine; D012995:Solubility
D000577:Amides; D000779:Anesthetics, Local; D008055:Lipids; D000077212:Ropivacaine; D008012:Lidocaine; D002045:Bupivacaine