Comparison of the in-vitro effect of several macrolides on the oxidative burst of human neutrophils.

We have compared the in-vitro interaction of five macrolides (roxithromycin, erythromycin, spiramycin, oleandomycin and josamycin) with human neutrophils (PMN). Only roxithromycin strongly impaired the oxidative burst of PMN assessed by luminol amplified chemiluminescence, superoxide anion generation, and myeloperoxidase-mediated iodination of proteins. This effect was observed only for high concentrations of this drug (100 and 50 mg/l). Furthermore, the sensitivity of PMN to the depressive effect of roxithromycin permitted the definition of two kinds of PMN: in Highly Sensitive (HS)-PMN, the oxidative response was completely abolished while in Moderately Sensitive (MS)-PMN, a decreased, but yet measurable (20-50% of the control), response was obtained. The roxithromycin-induced depression of PMN was time-dependent and partly reversed by washing. Chemotaxis was also impaired by roxithromycin (100 mg/l) but phagocytosis of Klebsiella pneumoniae was unaltered even at high concentrations of the drug. Since roxithromycin displays the highest intracellular uptake, compared with the other macrolides assessed in this study, this could explain the results observed here. The relevance to the clinical situation needs further study. This effect of roxithromycin could be useful to control the inflammatory process associated in certain infectious diseases, in particular if high concentrations of the drug are obtained in tissues.