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Published on: July 7, 2017
Fourteen-member macrolides inhibit interleukin-8 release by human eosinophils from atopic donors
T Kohyama1, H Takizawa, S Kawasaki
1Department of Medicine and Physical Therapy, School of Medicine, University of Tokyo, Japan.
Abstract:
Macrolide antibiotics such as erythromycin have been reported to be effective for asthma. However, the precise mechanisms of this effect remain unclear. We studied the effect of erythromycin, clarithromycin, josamycin, and other antibiotics on the release by eosinophils of interleukin-8 (IL-8), a potent chemokine for inflammatory cells, including eosinophils themselves. Human eosinophils were isolated from atopic patients, and the effects of the drugs on IL-8 release were evaluated. Only 14-member macrolides (erythromycin and clarithromycin) showed a concentration-dependent suppressive effect on IL-8 release (control, 100%; erythromycin at 1 microgram/ml, 67.82% +/- 3.45% [P < 0.01]; clarithromycin at 5 micrograms/ml, 56.81% +/- 9.61% [P < 0.01]). The effect was found at therapeutic concentrations and appeared to occur at the posttranscriprtional level. In contrast, a 16-member macrolide (josamycin) had no significant effect. We suggest that 14-member macrolides inhibit IL-8 release by eosinophils and may thereby prevent the autocrine cycle necessary for the recruitment of these cells into the airways.
Insights
Fourteen-member macrolide antibiotics like erythromycin suppress interleukin-8 (IL-8) release from eosinophils. This mechanism may explain their effectiveness in treating asthma by reducing inflammatory cell recruitment.
Area of Science:
- Immunology
- Pharmacology
- Respiratory Medicine
Background:
- Macrolide antibiotics, including erythromycin, show potential therapeutic benefits for asthma.
- The exact mechanisms underlying macrolides' efficacy in asthma management are not fully understood.
- Eosinophils play a crucial role in asthma pathogenesis through the release of inflammatory mediators like IL-8.
Purpose of the Study:
- To investigate the effects of specific macrolide antibiotics on interleukin-8 (IL-8) release from human eosinophils.
- To elucidate the potential mechanisms by which macrolides might modulate eosinophil-driven inflammation in asthma.
Main Methods:
- Isolation of human eosinophils from atopic patients.
- Incubation of eosinophils with various macrolide antibiotics (erythromycin, clarithromycin, josamycin) at different concentrations.
- Quantification of IL-8 release following antibiotic treatment.
Main Results:
- Fourteen-member macrolides (erythromycin, clarithromycin) demonstrated a concentration-dependent suppression of IL-8 release.
- Significant inhibition of IL-8 release was observed at therapeutic concentrations of erythromycin and clarithromycin.
- A 16-member macrolide (josamycin) did not exhibit a significant effect on IL-8 release.
- The suppressive effect appeared to occur at the post-transcriptional level.
Conclusions:
- Fourteen-member macrolides effectively inhibit IL-8 release from eosinophils.
- This inhibition may disrupt the autocrine signaling loop responsible for eosinophil recruitment into the airways.
- Macrolide-induced modulation of eosinophil IL-8 release offers a potential therapeutic strategy for asthma.

