EFFECTS OF VOLATILE ANESTHETICS ON HUMAN NEUTROPHIL OXIDATIVE RESPONSE TO THE BACTERIAL PEPTIDE FMLP

The oxidative burst response of neutrophils to bacteria is crucial for effective host defence. It has been shown that inhalation anaesthetic s 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 neutro phils after stimulation with the bacterial peptide, N-formyl-L-methion yl-L-leucyl-phenylalanine nine (FMLP) and phorbol-12-myristate-13-acet ate (PMA) was measured by oxidation of the indicator dye dihydrorhodam ine using flow cytometry. FMLP binds a specific surface receptor on ne utrophils and initiates via receptor specific signal transduction resp iratory burst as an all-or-none event, whereas PMA is an artificial ac tivator of protein kinase C, which bypasses receptor mediated signal t ransduction, In the presence of halothane, enflurane and sevoflurane, there was an increase in activation threshold on FMLP stimulation. Ove rall, this correlated with reduced H2O2 production, Isoflurane had no effect. In the presence of desflurane, however, H2O2 production of neu trophils increased two-fold, followed by transient suppression of neut rophil function. PMA-induced H2O2 generation was unchanged in the pres ence of volatile anaesthetics, We conclude that volatile anaesthetics modulated FMLP receptor-dependent signal transduction upstream of prot ein 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.