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Influence of ciprofloxacin on leukotriene generation from various cells in vitro
J Knöller1, J Brom, W Schönfeld
1Lehrstuhl für Medizinische Mikrobiologie und Immunologie, Ruhr Universität Bochum, FRG.
Abstract:
The effect of ciprofloxacin on leukotriene generation from human polymorphonuclear leucocytes (PMN) and the respective lymphocyte, monocyte and basophil (LMB) containing cell fraction has been studied. Furthermore, the influence on the LTB4-receptor expression of PMNL, as well as on the synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) from human platelets, was analysed. The antibiotic concentrations ranged from 0.5 to 4 micrograms/10(7) cells. Analysis of the generated leukotrienes was performed by high performance liquid chromatography (HPLC). The calcium-ionophore A23187 induced leukotriene generation from PMNs and LMBs was significantly suppressed by preincubation with ciprofloxacin in a dose-dependent manner. Incubation of PMNs with the same concentrations of ciprofloxacin induced an augmentation of the LTB4-receptor expression. Preincubation of human platelets led to a suppression of the calcium-ionophore induced 12-HETE generation at high concentrations (8 and 4 micrograms/10(8) cells) and to an increased synthesis of 12-HETE at lower concentrations (0.5, 1, and 2 micrograms ciprofloxacin/1 x 10(8) platelets).
Insights
Ciprofloxacin significantly suppresses leukotriene generation in human immune cells. However, it increases LTB4-receptor expression on polymorphonuclear leukocytes (PMNs) and affects 12-HETE synthesis in platelets.
Area of Science:
- Immunopharmacology
- Cellular Biology
Background:
- Leukotrienes play crucial roles in inflammatory responses.
- Polymorphonuclear leukocytes (PMNs) and other immune cells generate leukotrienes.
- Ciprofloxacin is a widely used antibiotic with potential immunomodulatory effects.
Purpose of the Study:
- To investigate the impact of ciprofloxacin on leukotriene generation from human PMNs and lymphocyte, monocyte, and basophil (LMB) fractions.
- To examine ciprofloxacin's influence on LTB4-receptor expression in PMNs.
- To analyze the effect of ciprofloxacin on 12-hydroxyeicosatetraenoic acid (12-HETE) synthesis in human platelets.
Main Methods:
- Human PMNs and LMB fractions were preincubated with varying concentrations of ciprofloxacin.
- Leukotriene generation was induced using the calcium-ionophore A23187.
- Analysis of leukotrienes was performed using high-performance liquid chromatography (HPLC).
- LTB4-receptor expression on PMNs and 12-HETE synthesis in platelets were also analyzed.
Main Results:
- Ciprofloxacin significantly suppressed calcium-ionophore-induced leukotriene generation from PMNs and LMBs in a dose-dependent manner.
- Incubation with ciprofloxacin led to an augmentation of LTB4-receptor expression on PMNs.
- Ciprofloxacin exhibited dual effects on 12-HETE synthesis in platelets: suppression at high concentrations and increased synthesis at lower concentrations.
Conclusions:
- Ciprofloxacin demonstrates immunomodulatory effects by suppressing leukotriene generation.
- The antibiotic influences inflammatory mediator pathways, including LTB4-receptor expression and 12-HETE synthesis.
- These findings suggest complex interactions between ciprofloxacin and human immune cell functions relevant to inflammation.