Roxythromycin Stimulates the Mucociliary Activity of the Eustachian Tube and Modulates Neutrophil Activity in the Healthy Guinea Pig

Abstract

Low-dosage, long-term erythromycin chemotherapy is useful in the treatment of chronic airway inflammatory diseases such as chronic sinusitis. The exact working mechanism of macrolides behind the clinical effectiveness still remains unclear. However, some have been considered including anti-inflammatory effect, effects on airway secretory functions, and steroid sparing effects. Otitis media with effusion (OME) is a chronic inflammatory disease in the tubotympanum. The epithelium of the tubotympanum is a modified respiratory epithelium. Therefore, macrolides might be effective in the treatment of patients with chronic OME. It was recently demonstrated that macrolides such as roxythromycin (RXM), enhance the ciliary activity in vitro. However, such ciliostimulatory effects found in an in vitro system are not always applicable to the mucociliary system in situ. The mucociliary system in situ might behave differently when in contact with RXM, and might deteriorate following oral administration of RXM. The present study aimed at investigating the in vivo effect of RXM on the mucociliary system in the tubotympanum and neutrophil activities of the guinea pig. The healthy guinea pigs were treated with oral administration of 5 or 50 mg/kg/day of RXM for 14 successive days, and the ciliary activity and the mucociliary clearance time of the tubotympanum was determined 24 h after the final administration. The ciliary activity in the Eustachian tube was significantly increased by oral administration of either dosage of RXM for 14 successive days. In addition, the mucociliary clearance velocity was accelerated by oral administration of such dosages of RXM. Therefore, the present data clearly demonstrate that RXM is a pharmacological agent with ciliostimulation and concurrent acceleration ability of the mucociliary clearance in the Eustachian tube. Oral administration of 5 as well as 50 mg/kg/day of RXM for 14 successive days did not significantly affect the phagocytosis activity of neutrophils but significantly increased the superoxide production of neutrophils. Since the effusions are considered to be the result of inflammatory events in the tubotympanum, the increased superoxide production activity of neutrophils confirmed in our study should result in an increased killing activity of infectious pathogens, thereby leading to control of the disease chronicity. In conclusion, our study argues in favor of the clinical usefulness of RXM in the treatment of OME.