Effect of RO 23-9424, cefotaxime and fleroxacin on functions of human polymorphonuclear cells and cytokine production by human monocytes

J Antimicrob Chemother. 1996 Nov;38(5):799-807. doi: 10.1093/jac/38.5.799.

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.

MeSH terms

  • Anti-Infective Agents / pharmacology
  • Cefotaxime / analogs & derivatives*
  • Cefotaxime / pharmacology*
  • Cephalosporins / pharmacology
  • Chemotaxis, Leukocyte / drug effects
  • Dose-Response Relationship, Drug
  • Fleroxacin / analogs & derivatives*
  • Fleroxacin / pharmacology*
  • Fluoroquinolones*
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-8 / metabolism
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Phagocytosis / drug effects
  • Superoxides / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Infective Agents
  • Cephalosporins
  • Fluoroquinolones
  • Interleukin-1
  • Interleukin-8
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Superoxides
  • Ro-23-9424
  • Cefotaxime
  • Fleroxacin