To elucidate the pathogenesis of otitis media with effusion (OME), the role of cytokines was investigated by analyzing the middle ear effusion (
MEE
) obtained from patients with this disease and from experimental animal models. Enzyme-linked immunosorbent assay (ELISA) of the
MEE
revealed that levels of IL-1β and IL-8 were higher in the mucoid type
MEE
than in the serous type
MEE
and were significantly increased in neutrophil-rich groups. Gene targets of those cytokines were also detected in pellets of the
MEE
by RT-PCR. However, the incidence of IL-6 and IL-8 detected by RT-PCR was lower than that detected by ELISA, suggesting that those cytokines were produced by the middle ear mucosa as well as inflammatory cells infiltrating the
MEE
.
In the animal experiment, OME was induced in mice by intra-tympanic inoculation with an endotoxin, and the levels of IL-1β in the
MEE
were significantly increased. Intra-tympanic inoculation with rIL-1β also produced the
MEE
and the cytological findings of the
MEE
as well as the histological findings of the middle ear mucosa were similar to those found in endotoxin-induced OME. Furthermore, an intra-tympanic injection with anti-IL-1 receptor antibodies reduced the incidence of OME induced by an endotoxin or rIL-1β, suggesting that IL-1β may play an important role in the pathogenesis of OME.
This clinical study demonstrated that macrolide was effective for OME and decreased the levels of inflammatory cytokines in the
MEE
including IL-1β and IL-8. Animal experiments also showed that co-administration of macrolide reduced the incidence of endotoxin-induced OME and the concentration of IL-1β in the
MEE
.
These findings suggest that cytokines play an important role in the pathogenesis of OME and that a cycle of the cytokine network might be associated with the persistence of this disease.
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