IN-VITRO INTERACTION BETWEEN SPIRAMYCIN AND POLYMORPHONUCLEAR NEUTROPHILS OXIDATIVE-METABOLISM

PMNs are a major component of body defense against microbial invasion, involving reactive oxygen species in great quantity, which could bene fit from antibiotic therapy. Recently, possible antibiotic effects on phagocyte functions (impairment or stimulation of reactive oxygen spec ies production) were studied. In our study, an in vitro evaluation was made on macrolide activity on phagocyte respiratory burst functions, using assay of superoxide anion (O .(-)(2)) in response to four stimul i systems: N-formyl Met-Leu-Phe (fMLP), an analogue of bacterial chemo tactic factors; 4 beta-phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C (PKC); calcium ionophore (A23187), whic h acts directly on calcium influx; and a bacterial strain, Staphylococ cus aureus. We have shown that spiramycin, at therapeutic plasma conce ntrations, increased O .(-)(2) generation by bacteria and fMLP-stimula ted PMNs, with rate of 26% for 1 mu g ml(-1) and 34% for 5 mu g ml(-1) , respectively. This pro-oxidant effect, however weaker, was observed when PMNs were stimulated by PMA. A weak anti-oxidant effect was obser ved with A23187. For higher concentrations, spiramycin decreased stron gly O .(-)(2) production, with IC50 values of 74 mu g ml(-1), 154 mu g ml(-1), 296 mu g ml(-1) and 400 mu g ml(-1) when PMNs were stimulated with bacteria, A23187, fMLP and PMA, respectively. The effect of spir amycin seemed to result from an intracellular mechanism by interventio n of PMN oxidative metabolism (NADPH-oxidase activation), rather than a simple chemical interaction, because no effect has been observed in acellular models. For higher spiramycin concentrations, the decrease o f O .(-)(2) production observed could not be taken into consideration because this concentration was not used in therapy. The enhanced of O .(-)(2) production observed could be used in therapy, so as to increas e PMNs bactericidal activity. (C) 1998 The Italian Pharmacological Soc iety.