Maeda Kazuhiko, Hirano Takashi, Ichimiya Issei, Kurono Yuichi, Suzuki Masashi, Mogi Goro
Department of Otolaryngology, Faculty of Medicine, Oita University, Japan.
Laryngoscope. 2004 Nov;114(11):1967-72. doi: 10.1097/01.mlg.0000147930.29261.51.
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).
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.
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.
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.
尽管中耳积液（OME）在儿童和成人中仍然是一种常见疾病，但其发病机制尚未完全明确。我们研究了向鼓室内注射从不可分型流感嗜血杆菌中纯化的内毒素对中耳积液（MEE）特征的影响。
通过堵塞咽鼓管（ET）建立OME小鼠模型，随后向鼓室内接种内毒素（内毒素组）或生理盐水（对照组）。在注射后3天、2周和2个月处死小鼠，检查MEE中的组织学变化和炎性细胞因子的产生情况。
所有小鼠在ET堵塞后2个月内均表现为OME。对照组的大多数MEE为浆液性，而黏液性或脓性MEE仅在内毒素组中发现。内毒素组中耳黏膜的上皮下间隙严重增厚，有大量单核细胞浸润。在所有时间点，内毒素组MEE中肿瘤坏死因子-α（TNF-α）的水平均显著高于对照组。此外，原位杂交显示TNF-α信使核糖核酸不仅在MEE中的白细胞和巨噬细胞中表达，而且在中耳黏膜上皮下间隙中的单核细胞中也有表达。
这些结果表明，ET堵塞对于浆液性MEE的诱导至关重要，额外给予内毒素与黏液性MEE的产生有关，同时伴有鼓室中炎性细胞浸润和细胞因子产生的组织学变化。
