In vitro activity of aminoglycosides on the respiratory burst response in human polymorphonuclear neutrophils

In response to phagocytosis of microbes or chemical stimuli, neutrophils generate reactive oxygen species which represent the major bactericidal mechanism of these cells. We have investigated the influence of aminoglycosides (amikacin, gentamicin, netilmicin and tobramycin), antibiotics with a marked concentration-dependent killing effect, on the human neutrophil oxidative burst represented by the release of hydrogen peroxide. This study was performed using time-dependent cellular experiments and a cell-free system. In the cellular model, 2-h incubation with amikacin (ranging from 10 mg/l to 1 g/l), enhanced hydrogen peroxide release by stimulated human neutrophils. At higher concentrations (1 to 5 g/l), hydrogen peroxide production was decreased. No significant effects were observed with the other aminoglycosides at concentrations ranging from 10 mg/l to 2.5 g/l. The pro-oxidant activity of amikacin may be due to a cellular mechanism through oxidative metabolism of human neutrophils as demonstrated in the cell washing experiment, whereas the antioxidant activity observed for higher concentrations may be a result of a scavenging effect as demonstrated in the cell-free system. The enhanced of hydrogen peroxide production observed for therapeutic concentrations of amikacin could be a beneficial effect for neutrophil bactericidal functions.