Effects of quinolones on interleukin 1 production in vitro by human monocytes.
The new quinoline derivative antibiotics (quinolones), pefloxacin and ciprofloxacin at concentrations higher than 50 micrograms/ml inhibit the PHA response of the human mononuclear leukocytes in vitro. Since monocytes have been shown to be accessory cells for the activation of lymphocytes by mitogens, we investigated the effects of pefloxacin and ciprofloxacin on extracellular interleukin 1 (IL-1) and cell-associated IL-1 from lipopolysaccharide-stimulated human monocytes. Pefloxacin and ciprofloxacin decreased the extracellular IL-1 in a dose-dependent manner, while cell-associated IL-1 was not altered. These effects were observed even after a short period of incubation (1 or 2 h). No inhibitory activity against purified IL-1 or IL-2 could be demonstrated in the dialyzed supernatants from pefloxacin- or ciprofloxacin-treated monocytes. Neither pefloxacin nor ciprofloxacin modified the biological activity of preformed IL-1. The decrease of extracellular IL-1 induced by pefloxacin and ciprofloxacin could, in part, account for the observed decrease in the proliferative response of human mononuclear leukocytes to phytohemagglutinin, as extracellular IL-1 and proliferative response were positively correlated (at various concentrations of pefloxacin and ciprofloxacin). The decrease in extracellular IL-1 was not associated with any alteration in the expression of the HLA-DR antigen on the monocytes membrane. These data suggested that pefloxacin and ciprofloxacin could antagonize IL-1 production and release by lipopolysaccharide-stimulated monocytes. These quinolones could be interesting tools to study the production, processing, transport and release from the monocytes of IL-1.
D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D007700:Kinetics; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009643:Norfloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015366:Pefloxacin; D010406:Penicillins / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors
D000890:Anti-Infective Agents; D006684:HLA-DR Antigens; D007375:Interleukin-1; D010406:Penicillins; D010835:Phytohemagglutinins; D015366:Pefloxacin; D002939:Ciprofloxacin; D009643:Norfloxacin