engleski

Azithromycin and resting host defense mechanisms in healthy human subjects

Macrolide antibiotics are used widely to treat bacterial infections. Increasing evidence suggests that they may also affect host defence mechanisms. To distinguish between anti-bacterial actions and effects on leukocytes and baseline inflammatory mediator production, we initiated a pilot study on the effects of azithromycin (AZ) in healthy human volunteers. Twelve healthy volunteers received standard AZ therapy (3 consecutive days 500 mg AZ, orally) and a battery of some 40 hematological and biochemical variables was chosen according to their relevance to the inflammatory process. Variables were measured immediately before AZ treatment (baseline), 2h after last dose (peak plasma conc.), 24 h after last dose (peak intracellular conc.) and 28 days after last dose (wash-out period). We observed an initial neutrophil degranulation effect of AZ, reflected in a rapid decrease, between 2 and 24 h, in the activities of b-glucuronidase, N-acetyl-b-D-glucosaminidase and myeloperoxidase and a corresponding increase in serum activities of these enzymes. The oxidative response to a perticulate stimulus was also acutely enhanced. These actions could facilitate anti-bacterial effects of AZ. A fall in interleukin-8 and interleukin-6 serum conc. in all volunteers was seen 3 and 24 h after the last dose of AZ and a similar, but more moderate trend was seen for GRO-a and sVCAM serum conc., as well as acute phase proteins. All cytokine concentrations remined within the non-pathological range. Based on morphology and in agreement with published in vitro data, apoptosis of neutrophils increased up to 28 days after the last AZ dose. Neutrophils isolated from blood at this time point also showed a delayed down-regulation of the oxidative burst, due to antibiotic treatment. These data indicate that AZ may exert modulatory effects on host defence mechanisms that could be of benefit in non-infective inflammatory conditions.

Azithromycin; host defense mechanisms; healthy human subjects

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