Biphasic modulation by azithromycin of human neutrophil function: implications for therapy
Abstract number: 10.1111/j.1198-743X.2004.902_s227.x
Modulatory effects of macrolide antibiotics on leucocyte function have been observed by a number of investigators. Relatively few studies have been performed, however, with azithromycin and its effects on leucocytes in vitro have been confusing. As the ability of azithromycin to accumulate in leucocytes is much greater than that of other macrolides, a study was performed to investigate the effects of a standard 3-day treatment with azithromycin (500 mg/day, p.o.) on a variety of leucocyte functions and circulating mediators in 12 healthy volunteers. Blood was taken 1 h before treatment, 2.5 h, 24 h and 28 days after the last dose. An initial neutrophil degranulating effect of azithromycin was reflected in rapid decreases in azurophilic granule enzyme activities in cells and corresponding increases in serum. The oxidative response to a particulate stimulus was also acutely enhanced. These actions were associated with high plasma and neutrophil drug concentrations. It seems likely that this acute stimulation of leukocyte function, also observed in some in vitro studies, may facilitate anti-bacterial effects of azithromycin. A continuous fall, in response to azithromycin treatment, in chemokine and interleukin-6 serum concentrations, within the non-pathological range, was accompanied by a delayed down-regulation of the oxidative burst and an increase in apoptosis of neutrophils up to 28 days after the last azithromycin dose. Neutrophils isolated from blood at this time point still contained detectable drug concentrations. This delayed, potentially anti-inflammatory activity may curtail deleterious inflammation during recovery from an infection. In a more recent study, using the same azithromycin treatment schedule in patients with chronic obstructive pulmonary disease, reductions in circulating leucocytes and in acute phase proteins were found that would appear to support the potential for azithromycin to exert anti-inflammatory effects."
|Session name:||XXIst ISTH Congress|
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