title: Erythromycin shortens neutrophil survival by accelerating apoptosis.
abstract: Erythromycin is reported to have an anti-inflammatory action, which may account for its clinical effectiveness in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To evaluate the anti-inflammatory action of erythromycin, we examined the survival of isolated neutrophils with and without erythromycin. Erythromycin shortened neutrophil survival in a dose-dependent fashion, with a maximum effect at 10 micrograms/ml [corrected] and above. Survival at 24 h was 63.4% in medium with 10 micrograms of erythromycin per ml compared with 82.7% in control medium (P < 0.01). This shortening of survival was brought about by acceleration of apoptosis, as evidenced by transmission electron microscopy. In a manner similar to that of erythromycin, other macrolide antibiotics, i.e., clarithromycin, roxithromycin, and midecamycin, also shortened neutrophil survival, but neither the beta-lactams ampicillin and cefazolin nor the aminoglycoside gentamicin affected their survival. Erythromycin increased intracellular levels of cyclic AMP (cAMP) to 150% of control levels in neutrophils. Forskolin, rolipram, and dibutyryl-cAMP, which are known to increase intracellular cAMP levels, also shortened neutrophil survival. H-89, an inhibitor of cAMP-dependent protein kinase A, partially blocked the survival-shortening effect of erythromycin. Our findings suggest that erythromycin shortens neutrophil survival at least in part through elevation of intracellular cAMP levels.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical College, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Aoshiba
authors.forename: A
authors.initials: A
authors.lastname: Nagai
authors.forename: K
authors.initials: K
authors.lastname: Konno
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004917:Erythromycin / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004917:Erythromycin; D000242:Cyclic AMP