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The effect of erythromycin on Pseudomonas aeruginosa and neutrophil mediated epithelial damage
E Tanaka1, K Kanthakumar, D R Cundell
1Host Defence Unit, National Heart & Lung Institute, London, UK.
Abstract:
Erythromycin therapy for long periods may benefit patients with chronic bronchial sepsis colonized by Pseudomonas aeruginosa despite the lack of antibacterial activity. We have investigated the effect of filtrates of 24 h P. aeruginosa cultures (CF) with or without erythromycin 0.5, 5, 20 mg/L on human nasal epithelium in the absence or presence of polymorphonuclear leucocytes (PMN). Ciliary beat frequency (CBF) and epithelium integrity were examined for 4 h. Erythromycin (20 mg/L) alone did not affect epithelium. CF without erythromycin slowed CBF by 63.5% of control at 4 h, and caused disruption of surface integrity in 80% of the epithelium. Addition of erythromycin to CF did not inhibit these effects. Erythromycin did not affect growth of P. aeruginosa. Filtrates of P. aeruginosa cultured with erythromycin (5 and 20 mg/L) caused less CBF slowing (37.2% and 19.2% of control, respectively) and epithelial disruption (4.2% and 6.7%, respectively). Unstimulated PMN (10(7)/mL) slowed CBF by 13% of control at 4 h but did not cause epithelial disruption. PMN and CF together slowed CBF (95.4% of control) and damaged epithelium (93.3% of epithelium disrupted) synergically. Pre-incubation of PMN with erythromycin did not inhibit these effects. PMN and filtrates of P. aeruginosa cultured with erythromycin (5 and 20 mg/L) caused less CBF slowing (58.0% and 33.6% of control, respectively) and epithelial disruption (40.0% and 13.3%, respectively). Erythromycin may benefit patients by reducing P. aeruginosa production of factors which damage epithelium and stimulate neutrophil mediated cytotoxicity.
Insights
Erythromycin may help chronic bronchial sepsis patients by reducing Pseudomonas aeruginosa
Area of Science:
- Respiratory Medicine
- Microbiology
- Cell Biology
Background:
- Chronic bronchial sepsis often involves Pseudomonas aeruginosa.
- Erythromycin's long-term benefits in such cases are unclear, despite limited direct antibacterial activity.
- The study explores erythromycin's non-antibacterial effects on airway epithelium and immune cells.
Purpose of the Study:
- To investigate erythromycin's impact on human nasal epithelium and polymorphonuclear leukocytes (PMN) when exposed to Pseudomonas aeruginosa.
- To determine if erythromycin modulates the cytotoxic effects of P. aeruginosa and PMN on airway tissues.
Main Methods:
- Human nasal epithelial cells were exposed to Pseudomonas aeruginosa culture filtrates (CF) with or without erythromycin.
- Ciliary beat frequency (CBF) and epithelial integrity were assessed over 4 hours.
- The effects were also studied in the presence of polymorphonuclear leukocytes (PMN).
Main Results:
- Pseudomonas aeruginosa CF significantly reduced CBF and damaged epithelial integrity.
- Erythromycin alone did not harm the epithelium but reduced P. aeruginosa's cytotoxic effects when co-cultured.
- PMN synergistically worsened epithelial damage and reduced CBF in the presence of P. aeruginosa CF, an effect partially mitigated by pre-culturing P. aeruginosa with erythromycin.
Conclusions:
- Erythromycin may benefit patients with chronic bronchial sepsis by reducing Pseudomonas aeruginosa's production of factors that damage airway epithelium.
- Erythromycin also appears to reduce the cytotoxic effects of neutrophils stimulated by P. aeruginosa.
- These findings suggest a role for erythromycin beyond its direct antibacterial action in managing chronic respiratory infections.