title: Effect of RO 23-9424, cefotaxime and fleroxacin on functions of human polymorphonuclear cells and cytokine production by human monocytes.
abstract: The way in which an antibiotic interacts with host defences could influence the clinical outcome of many infectious diseases. The impact of RO 23-9424, a novel dual-action and extended-spectrum antibiotic, was studied on several functions of human polymorphonuclear neutrophils (PMNs). A significant (P < 0.05) increase of the superoxide (O2-) released by phorbol-myristate acetate (PMA) -stimulated PMN (10-100 mg/L) can be observed in the RO 23-9424 pre-treated cells. RO 23-9424, particularly at low dosages, showed an interesting but not statistically significant effect on PMN phagocytosis. Higher dosages of RO 23-9424 (50-200 mg/L) and fleroxacin (20-200 mg/L) significantly reduced PMN chemotaxis. Cytokine production by human monocytes were also evaluated after incubation with the antibiotic (100-200 mg/L) in both basal conditions and in response to endotoxin (lipopolysaccharide, LPS). In the LPS-treated cells, RO 23-9424 (100 mg/L) significantly (P < 0.05) enhanced the tumour necrosis factor-alpha (TNF-alpha) levels, compared with LPS controls after 4 h of incubation. RO 23-9424 (200 mg/L) was able to reduce in a dose-dependent way LPS-induced interleukin-1 beta (IL-1 beta) after 4 and 24 h of incubation. Interleukin-8 (IL-8) release was not significantly changed by RO 23-9424. Cefotaxime (200 mg/L) significantly (P < 0.05) increased the basal levels of IL-1 beta and reduced basal IL-8 concentration after 24 h of incubation. The lower concentration of cefotaxime reduced the LPS-stimulated IL-8 levels. Fleroxacin (100 mg/L) enhanced basal levels of IL-8. The potentiated PMN phagocytosis, the significantly enhanced O2- release by PMA-stimulated PMN and the dimetric changes of TNF-alpha and IL-1 beta appeared peculiar for RO 23-9424 and may have useful therapeutical implications.
authors.affiliation: Department of Microbiological, Neurological and Orthopaedic Sciences, University of Reggio Calabria, Cantanzaro, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Matera
authors.forename: M C
authors.initials: MC
authors.lastname: Berlinghieri
authors.forename: F
authors.initials: F
authors.lastname: Foti
authors.forename: G S
authors.initials: GS
authors.lastname: Barreca
authors.forename: A
authors.initials: A
authors.lastname: Focà
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016576:Fleroxacin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D024841:Fluoroquinolones; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C060441:Ro-23-9424; D002439:Cefotaxime; D016576:Fleroxacin