マクロライドと気道防御機能 マクロライドと粘液分泌

Abstract

In the present study, we examined the in vivo and in vitro effects of erythromycin (EM) on epithelial mucus production. We produced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by the intranasal instillation of endotoxin. The in vivo effects of EM on epithelial mucus production were studied using this animal model. Intraperitoneal injection of EM (100 mg/kg body weight × 8 days), ampicillin (ABPC, 200 mg/kg body weight × 8 days), and cefalotin (CET, 200 mg/kg body weight × 8 days) inhibited epithelial mucus production induced after 7 days of endotoxin instillation. EM had a greater inhibitory effect than ABPC or CET.The in vivo effects of EM on epithelial mucus secretion were studied using cultured human nasal epithelial cells. Mucus secretion was quantitatively measured by the monoclonal antibody HCS18, which specifically reacts with mucin-like materials in human epithelial goblet cells. The spontaneous mucus secretion from cultured epithelial cells did not change after incubation with 10-4 to 10-6 M EM, 10-4 M ABPC, or 10-4 M CET.These results indicate that EM has a greater inhibitory effect on endotoxin-induced epithelial mucus production than ABPC or CET, and that this effect is not caused by the direct action of EM on epithelial secretory cells.