The influence of intravenous anaesthetics on the activity of enzymes released from polymorphonuclear leucocytes in vitro.
OBJECTIVE
Polymorphonuclear leucocytes make a decisive contribution to defence against bacterial infections. In particular, the effects of anaesthetics on non-oxidative bactericidal mechanisms have previously only been superficially examined. Although the influence of anaesthetic agents on oxidative bactericidal activity has been thoroughly examined, our study concentrated on the effect on non-oxidative processes, which appears to have been a neglected field of research.


METHODS
The effects of methohexital, etomidate, ketamine, fentanyl and morphine on the activity of lysozyme and beta-glucuronidase released from polymorphonuclear leucocytes have been studied in vitro. The activity of lysozyme was determined by recording the changes in the turbidity of a suspension of micrococcus lysodeicticus caused by the enzymatic action of lysozyme. beta-glucuronidase activity was photometrically measured by the enzymatic cleavage of phenolphthalein glucuronic acid.


RESULTS
High concentrations of methohexital inhibited lysozyme activity; however, etomidate and morphine caused an increase of beta-glucuronidase activity in therapeutic plasma concentrations. While there was no effect of etomidate on lysozyme activity, all concentrations tested significantly stimulated beta-glucuronidase activity. This result was unexpected because intravenous anaesthetics have previously shown a tendency to suppress polymorphonuclear leucocyte functions. Whereas the inhibition of lysozyme activity by the high concentration of methohexital was no surprise, the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine was quite unexpected.


CONCLUSIONS
At present, the underlying mechanism for the increase of beta-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The fact that there was no influence of these agents on lysozyme activity possibly suggests that the anaesthetic agents have different effects on azurophilic and specific granules. Since in vitro investigations have their limitations, it is too early to draw practical consequences from our study. Moreover, at present it is unclear whether an increase of beta-glucuronidase activity in vivo is an advantage or not. In any case, we think it advisable to perform further investigations on the influence of anaesthetic agents on oxygen-independent bactericidal mechanisms.
Krumholz
W
W
Department of Anaesthesiology and Intensive Care Medicine, Bethlehem-Hospital, Stolberg, Germany.
Weidenbusch
H
H
Menges
T
T
Keller
G
G
Hempelmann
G
G
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002469:Cell Separation; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*
D018686:Anesthetics, Intravenous; D009113:Muramidase; D005966:Glucuronidase