Effects of rokitamycin on phagocytosis and release of oxidant radicals of human polymorphonuclear leukocytes.
A rational choice of an antimicrobial agent must take into account not only the activity against the specific pathogen but also any possible negative or positive effects on the host defense system. Rokitamycin (RKM) is an orally active 16-membered-ring macrolide; there are no reports of specific investigations of these activities in the literature. Polymorphonuclear neutrophils (PMNs) from healthy adult donors were incubated in medium alone or in medium containing increasing concentrations (1, 10, 50, 100 micrograms/ml) of RKM. In unwashed PMNs phagocytosis was unaffected by RKM, while luminol-amplified chemiluminescence (LACL) was significantly reduced by 50 and 100 micrograms/ml. When PMNs were washed after incubation phagocytosis was not modified but LACL was significantly restored. These characteristics of RKM were similar to those of roxithromycin and can be put in correlation with the cellular/extracellular ratio (30.5 for PMNs and 120 for macrophages) that was similar to that of roxithromycin but higher than of other macrolides. The molecular mechanisms by which high concentrations of these two macrolides produce such an impairment of LACL are still unclear. RKM has no unwanted effects on PMNs because the serum concentrations that can be obtained with the highest doses administered to man are lower than the concentrations which did not affect PMN functions in our study.
Braga
P C
PC
Department of Pharmacology, School of Medicine, University of Milan, Italy.
Maci
S
S
Dal Sasso
M
M
Fonti
E
E
Ghessi
A
A
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D015644:Miocamycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D005609:Free Radicals; D015644:Miocamycin; C033383:rokitamycin