Influenza A virus-induced otitis media and mucociliary dysfunction in the guinea pig.

There is much epidemiologic, clinical and laboratory evidence that viral infection is involved in otitis media with effusion (OME). However, few studies have demonstrated any direct influence of viruses on the tubotympanum. The purpose of this study was to establish the effect of influenza A virus having invaded the tubotympanum and so elucidate the possible mechanism by which this virus contributes to the pathogenesis of OME. Eighty guinea pigs with normal otoscopic findings were inoculated with 0.2 ml suspension of influenza A (3.3 x 10(8) PFU/ml) into the tympanic cavity through the tympanic membrane. To serve as controls, the same number of guinea pigs were injected with 0.2 ml of physiologic saline solution into the tympanic cavity. At 3, 7, 14, and 28 days postinoculation, they were used for examination of the mucociliary function. Middle ear effusions as well as mucociliary dysfunction were observed only in the animals inoculated with the virus. The ciliary activity in the bulla was declined at any time examined. On the other hand, the ciliary activity in the Eustachian tube and the tympanic orifice was slightly lowered between 7 and 14 days, but the level was not different from that of the controls. However, the number of active ciliated cells (showing more than 500 beats/min) was significantly smaller than that of the controls. The mucociliary clearance time of the tubotympanum was more prolonged than that of the controls at 3, 7, and 14 days, and returned to the control level at 28 days. A variety of morphological changes were observed in the tubotympanum treated with the virus. Major pathologies observed included general inflammatory cell infiltration, vacuolation and other degeneration of ciliated cells, and vascular damage and increased vascular permeability. Regeneration of cilia or ciliated cells followed the degeneration, which included an increased number of basal cells and newly formed centrioles. However, the viral infection also affected the epithelial cells with new centrioles. Our study demonstrates that viral infection can evoke mucociliary dysfunction of the tubotympanum and create increased susceptibility to bacteria. Therefore, viral infection may enhance bacterial infectious processes in the tubotympanu thereby contributing to the occurrence of OME.