Cytokine expression in experimental chronic otitis media with effusion in mice.

Objectives: Although otitis media with effusion (OME) is still a common disease in children and adults, the pathogenesis is not yet fully understood. We studied the effects of intratympanic injection with endotoxin purified from nontypeable Haemophilus influenzae on the characteristics of middle ear effusion (MEE). Methods: Murine model of OME was developed by eustachian tube (ET) blockage followed by intratympanic inoculation with endotoxin (endotoxin group) or saline (control group). The mice were decapitated and histological changes and the production of inflammatory cytokines in MEEs were examined 3 days, 2 weeks, and 2 months after injection. Results: All mice showed OME until 2 months after ET blockage. Most MEEs in the control group were serous, and mucoid or pultaceous MEEs were found only in the endotoxin group. Subepithelial space of middle ear mucosa was severely thickened with the infiltration of a large number of mononuclear cells in the endotoxin group. The levels of tumor necrosis factor-α (TNF-α) in MEEs were significantly higher in the endotoxin group than in the control group at all time points. Further, in situ hybridization showed that TNF-α messenger RNA was expressed not only by leukocytes and macrophages in MEEs but mononuclear cells present in the subepithelial space of middle ear mucosa. Conclusions: These results indicate that ET blockage is essential for the induction of serous MEE and additional administration of endotoxin is associated with the production of mucoid MEE accompanied by histological changes with inflammatory cell infiltration and cytokine production in the tympanic cavity.