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Erythromycin inhibits beta2-integrins (CD11b/CD18) expression, interleukin-8 release and intracellular oxidative
1Department of Thoracic Medicine II, Chang Gung Memorial Hospital, Taipei, Taiwan.
Abstract:
Macrolides have therapeutic benefits on chronic inflammatory airway diseases. Thus, macrolides are supposed to have variable biological effects apart from antimicrobial activity. Neutrophil adherence and influx with oxidants and cytokines production implicates involvement in airway inflammation. To investigate whether erythromycin (EM) affects neutrophil activity in vitro, lipopolysaccharide (LPS)-treated neutrophils were continuously incubated for 4 h in the absence or presence of increasing doses of EM from 1 microg ml(-1) to 100 microg ml(-1) in the last 2 h. Leukocyte adhesion molecules Mac-1 and intracellular H2O2(DCFH) were determined by flowcytometric assay. IL-8 and TNFalpha in supernatant was measured by ELISA method. The expression of Mac-1 and mean intracellular DCF fluorescence intensity (DCFH) of neutrophils significantly increased after stimulation with LPS. Pretreatment with EM significantly decreased LPS induced Mac-1 expression on neutrophils compared with LPS stimulation only. EM alone (100 microg ml(-1)) also decreased Mac-1 expression on neutrophils. EM significantly reduced the LPS-increased DCFH. EM alone (100 microg ml(-1)) also caused a decrease in DCFH. Increasing doses of EM also significantly decreased the IL-8 released by LPS-stimulated neutrophils. In conclusion, EM exerts a direct effect on the neutrophils by downregulating the expression of beta2-integrin on neutrophils, thus leading to a decrease in the intracellular H2O2, as well as the production of IL-8. Our conclusion provides an explanation for the clinical efficacy of erythromycin in neutrophil-mediated airway inflammation.
Insights
Erythromycin (EM) reduces neutrophil activity in airway inflammation by decreasing Mac-1 expression and inflammatory cytokine production. This macrolide
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Macrolides offer therapeutic benefits for chronic inflammatory airway diseases.
- Neutrophil adherence, oxidant production, and cytokine release are key factors in airway inflammation.
- Erythromycin (EM) may possess anti-inflammatory effects beyond its antimicrobial properties.
Purpose of the Study:
- To investigate the in vitro effects of erythromycin (EM) on neutrophil activity.
- To determine if EM modulates neutrophil adherence molecules and inflammatory mediator release.
Main Methods:
- Neutrophils were stimulated with lipopolysaccharide (LPS) and incubated with varying doses of EM.
- Flow cytometry assessed Mac-1 expression and intracellular hydrogen peroxide (H2O2) levels (DCFH).
- ELISA measured Interleukin-8 (IL-8) and Tumor Necrosis Factor-alpha (TNFα) in the supernatant.
Main Results:
- LPS stimulation significantly increased Mac-1 expression and H2O2 production in neutrophils.
- EM pretreatment significantly reduced LPS-induced Mac-1 expression and H2O2 levels.
- EM dose-dependently decreased IL-8 release from LPS-stimulated neutrophils.
Conclusions:
- Erythromycin directly impacts neutrophils by downregulating beta2-integrin (Mac-1) expression.
- EM reduces intracellular H2O2 production and IL-8 release in neutrophils.
- These findings explain the clinical efficacy of erythromycin in neutrophil-mediated airway inflammation.