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.