[The role of IL-1 beta in murine model of otitis media with effusion].
Recent studies have demonstrated the presence of inflammatory cytokines such as IL-1 beta, TNF-alpha, IL-6, and IL-8 in the middle ear effusion (MEE) of patients with otitis media with effusion (OME). IL-1 beta is known to be produced from macrophages and monocytes in an early stage of inflammation by stimulation with microorganisms and endotoxins. Also, these studies have shown that endotoxins frequently are found in MEE and can induce OME in experimental animal model. These findings suggest that endotoxins in MEE cause a chain reaction of cytokines through IL-1 beta. However, the precise role of IL-1 beta in the pathogenesis of OME has not yet been clarified. In the present study, a murine model of OME was developed by intra-tympanic injection with endotoxin or recombinant mouse IL-1 beta (rIL-1 beta) and the effects of IL-1 beta on the production of MEE were investigated. OME was induced in specific pathogen-free male BALB/c mice by intra-tympanic inoculation with endotoxin purified from nontypeable Haemophilus influenzae or with rIL-1 beta. The presence of MEE in the subjects was observed through the ear drum under a microscope and samples of MEE were collected by aspiration and washing with phosphate-buffered saline. The concentrations of IL-1 beta in each sample of MEE were determined by ELISA and the histological changes were compared. The mice inoculated with endotoxin showed signs of the production of MEE and it was noted that the levels of IL-1 beta in MEE were significantly increased on day 3. Intra-tympanic inoculation with rIL-1 beta also produced MEE and these cytological findings of MEE as well as the histological findings of middle ear mucosa were similar to those found in the endotoxin-induced OME. Further, the influence of anti-IL-1 receptor antibodies on the production of OME was examined 3 days after intra-tympanic injection with anti-IL-1 receptor antibodies together with endotoxin or rIL-1 beta. The incidence of OME was lower in mice injected with anti-IL-1 receptor antibodies than that in mice injected with endotoxin or rIL-1 beta only. These findings suggest that IL-1 beta may play an important role in the pathogenesis of OME.
Kurono
Y
Y
Department of Otolaryngology, Faculty of Medicine, Kagoshima University.
Hirono
T
T
Watanabe
T
T
Suzuki
M
M
Mogi
G
G
D000818:Animals; D004731:Endotoxins; D007375:Interleukin-1 / Q000032:analysis / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010034:Otitis Media with Effusion / Q000209:etiology / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology
D004731:Endotoxins; D007375:Interleukin-1; D011994:Recombinant Proteins