The effect of erythromycin on Pseudomonas aeruginosa and neutrophil mediated epithelial damage.
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.
Tanaka
E
E
Host Defence Unit, National Heart & Lung Institute, London, UK.
Kanthakumar
K
K
Cundell
D R
DR
Tsang
K W
KW
Taylor
G W
GW
Kuze
F
F
Cole
P J
PJ
Wilson
R
R
D001427:Bacterial Toxins / Q000096:biosynthesis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D009079:Mucociliary Clearance / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism
D001427:Bacterial Toxins; D004917:Erythromycin