Roxythromycin Prevents Endotoxin-induced Otitis Media with Effusion in the Guinea Pig

Abstract

Pharmacological agents that can normalize or enhance the ciliary and mucociliary activity of the tubotympanum should also be able to break the vicious circle of chronic otitis media with effusion (OME). Roxythromycin (RXM) has been shown to enhance the ciliary activity in vitro and also stimulate the mucociliary activity in vivo and may therefore, when clinically applied, prevent not only occurrence but also recurrence of clinical OME. The present study was designed to discuss the possible preventive effect of RXM on endotoxin-induced OME in the guinea pig. A total of 120 guinea pigs were used. The normal control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 5 and 50 mg/kg of sairei-to for 14 successive days, respectively. Then, the saline-control group, the low-dosage group and the high-dosage group were treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 μg/ml) derived from Klebsiella pneumoniae. All 10 animals in the four groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions was significantly reduced in the low-dosage and high-dosage groups. Throughout the observation period, the ciliary activity in the tubotympanum was significantly reduced in the saline-control group as compared with that of the normal control group. By contrast, the ciliary activity in the low-dosage and high-dosage groups was not so reduced in the Eustachian tube and the middle ear close to the orifice. Mucociliary clearance time in the low-dosage and high-dosage groups was not different from that in the normal control group throughout the period. The tubotympanum in the saline-control group exhibited mucosal pathologies characteristic of OME in human. By contrast, the low-dosage and high-dosage groups exhibited much milder pathological changes in the tubotympanum than those in the saline-control group. In conclusion, clinical application of RXM could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially in OME-prone individuals.

Key Words:

• ciliary activity
• mucociliary clearance
• tubotympanum
• endotoxin
• macrolide
• roxythromycin
• otitis media with effusion.