Vol. 93 No.4 April 2000
The
Role of Cytokines in Otitis Media
Yuichi
Kurono (Wakayama
Medical College)
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.
Key
words: cytokine,
otitis media with effusion, middle ear effusion, endotoxin, macrolide