In vitro effects of spiramycin and dirithromycin on IL1 beta production by human LPS-stimulated mononuclear cells
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Published on: March 1, 2011
I Moutard1, B Gressier, F Bonte
1Laboratoire de Pharmacologie, Pharmacocinétique et Pharmacie Clinique, Faculté des Sciences Pharmaceutiques et Biologiques de Lille, France.
Abstract:
Polymorphonuclear neutrophils are the predominant cells in acute inflammatory lesions and their functions and recruitment are regulated by cytokines, including IL1, TNF and IL8. Antibiotic modulation of inflammatory effects has stimulated investigations of antibiotics for their potential activity as immunomodulators over their primary bactericidal or bacteriostatic activities. This study reports the influence of macrolides, spiramycin and dirithromycin on IL1 beta production. Mononuclear cells, isolated from healthy human volunteers, were preincubated with macrolides (0.1 to 500 micrograms/ml) and stimulated by Escherichia coli lipopolysaccharide. Then, IL1 beta production was detected by western blotting analysis. At therapeutic concentrations, dirithromycin and spiramycin seemed to enhance IL1 beta production by LPS-stimulated cells, with +37 per cent and +28 per cent at 1 microgram/ml respectively. At supratherapeutic concentrations, these drugs seemed to inhibit IL1 beta production through protein kinase C inhibition, with inhibitory concentrations 50 per cent of 378 micrograms/ml for dirithromycin and 234 micrograms/ml for spiramycin. So, macrolides may modulate the host defence system through their influence on cytokine production.
Insights
Macrolide antibiotics like spiramycin and dirithromycin can modulate the immune response by affecting interleukin-1 beta (IL1-β) production in immune cells. These antibiotics may enhance or inhibit IL1-β depending on their concentration.
Area of Science:
- Immunology
- Pharmacology
- Microbiology
Background:
- Polymorphonuclear neutrophils are key in acute inflammation, with functions regulated by cytokines like IL1, TNF, and IL8.
- Antibiotics are being investigated for immunomodulatory effects beyond their antimicrobial properties.
- Macrolides, including spiramycin and dirithromycin, are examined for their impact on cytokine production.
Purpose of the Study:
- To investigate the influence of macrolides (spiramycin and dirithromycin) on interleukin-1 beta (IL1-β) production.
- To determine if these macrolides act as immunomodulators by affecting cytokine synthesis.
Main Methods:
- Mononuclear cells from healthy volunteers were used.
- Cells were preincubated with varying concentrations of macrolides (0.1 to 500 µg/ml).
- Cells were stimulated with Escherichia coli lipopolysaccharide (LPS), and IL1-β production was measured via Western blotting.
Main Results:
- Therapeutic concentrations of dirithromycin and spiramycin enhanced IL1-β production by LPS-stimulated cells (+37% and +28% at 1 µg/ml, respectively).
- Supratherapeutic concentrations inhibited IL1-β production, potentially via protein kinase C inhibition.
- IC50 values for inhibition were 378 µg/ml for dirithromycin and 234 µg/ml for spiramycin.
Conclusions:
- Macrolides demonstrate immunomodulatory potential by influencing cytokine production.
- The effect of macrolides on IL1-β is concentration-dependent, showing enhancement at therapeutic levels and inhibition at higher concentrations.
- These findings suggest a dual role for macrolides in modulating the host defense system through cytokine modulation.
