title: Cytokine expression in experimental chronic otitis media with effusion in mice.
abstract: OBJECTIVE
  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-alpha (TNF-alpha) 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-alpha 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.
authors.affiliation: Department of Otolaryngology, Faculty of Medicine, Oita University, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirano
authors.forename: Issei
authors.initials: I
authors.lastname: Ichimiya
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kurono
authors.forename: Masashi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Goro
authors.initials: G
authors.lastname: Mogi
mesh_terms: D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010034:Otitis Media with Effusion / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines