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Effects of quinolones on interleukin 1 production in vitro by human monocytes
Abstract:
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.
Insights
New quinolone antibiotics, pefloxacin and ciprofloxacin, inhibit human immune cell responses by reducing interleukin-1 (IL-1) production. These findings offer insights into quinolone mechanisms and IL-1 regulation in monocytes.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Quinolone antibiotics, including pefloxacin and ciprofloxacin, can impact human immune cell function.
- Monocytes act as accessory cells, crucial for lymphocyte activation by mitogens.
- Interleukin-1 (IL-1) is a key cytokine involved in immune responses.
Purpose of the Study:
- To investigate the effects of pefloxacin and ciprofloxacin on IL-1 production and release by human monocytes.
- To determine if these quinolones interfere with IL-1's role in lymphocyte activation.
Main Methods:
- Human mononuclear leukocytes were exposed to pefloxacin and ciprofloxacin.
- Lipopolysaccharide-stimulated monocytes were analyzed for extracellular and cell-associated IL-1.
- Assays measured IL-1, IL-2 activity, and HLA-DR antigen expression.
Main Results:
- Pefloxacin and ciprofloxacin dose-dependently decreased extracellular IL-1 from stimulated monocytes.
- Cell-associated IL-1 and HLA-DR expression remained unaltered.
- No direct inhibition of IL-1 or IL-2 was observed, nor was the activity of preformed IL-1 affected.
Conclusions:
- Pefloxacin and ciprofloxacin antagonize IL-1 production and release by monocytes.
- The reduction in extracellular IL-1 may explain the observed inhibition of lymphocyte proliferation.
- These quinolones serve as valuable tools for studying IL-1 biology.