Effects of volatile anaesthetics on human neutrophil oxidative response to the bacterial peptide FMLP

Abstract

The oxidative burst response of neutrophils to bacteria is crucial for effective host defence. It has been shown that inhalation anaesthetics interfere with neutrophil function and the object of this study was to characterize the mechanisms of interaction of volatile anaesthetics with the oxidative response of neutrophils. H2O2 production by neutrophils after stimulation with the bacterial peptide, N-formyl-L-methionyl-L-leucyl-phenylalanine (FMLP) and phorbol-12-myristate-13-acetate (PMA) was measured by oxidation of the indicator dye dihydrorhodamine using flow cytometry. FMLP binds to a specific surface receptor on neutrophils and initiates via receptor specific signal transduction respiratory burst as an all-or-none event, whereas PMA is an artificial activator of protein kinase C, which bypasses receptor-mediated signal transduction. In the presence of halothane, enflurane and sevoflurane, there was an increase in activation threshold on FMLP stimulation. Overall, this correlated with reduced H2O2 production. Isoflurane had no effect. In the presence of desflurane, however, H2O2 production of neutrophils increased two-fold, followed by transient suppression of neutrophil function. PMA-induced H2O2 generation was unchanged in the presence of volatile anaesthetics. We conclude that volatile anaesthetics modulated FMLP receptor-dependent signal transduction upstream of protein kinase C activation, leading to a reduced response in the presence of halothane, enflurane and sevoflurane and to an increased response in the presence of desflurane.