Basic Immunological Study of Meniere's Desease

为了阐明Menier病的免疫学发病机制，我们采用了内耳免疫损伤的动物模型，研究了免疫活性细胞在内耳内募集的机制。该动物模型表现为自发性眼球震颤，在抗原直接攻击系统预敏豚鼠的囊后伴有内淋巴积水的波动听力损失。免疫活性细胞可以迁移到前庭和耳蜗区的远处，但抗原没有在这些区域扩散。干扰素-γ即刻产生，6h达高峰。干扰素-γ在前庭和耳蜗处也有表达，ICAM-1的表达在12h达到高峰。这些结果表明，在没有直接抗原刺激的情况下，囊中产生的炎性细胞因子刺激整个内耳表达ICAM-1，并诱导免疫细胞迁移到内耳。此外，细胞增殖发生在该动物模型的囊中。因此，内囊可能在内耳的免疫防御中起重要作用，并可能导致内耳免疫损伤的病因。内皮素-1(ET-1)在内耳的重要部位被发现，以维持水分平衡和感觉神经的转导。在这种动物模型中，ET-1的活性受到强烈的影响，提示ET-1在维持内耳微环境的动态平衡方面具有重要的作用。初步结果表明，淋巴细胞和PMN主要在外淋巴区迁移，而在其他器官中不迁移。用牛内耳组织进行Western印迹分析，发现与内耳疾病患者的血清反应有多条阳性条带。进一步的研究对于梅尼埃病的自身免疫病因学是至关重要的。

In order to elucidate an immunological pathogenesis of Menier's disease, we investigated the mechanism of recruitment of immunocompetent cells within the inner ear, employing an animal model of the inner ear immune injury. This animal model demonstrates spontaneous nystagmus, fluctuating hearing loss with endolymphatic hydrops following antigen challenge directly to the sac of systemically presensistized guinea pigs. Immunocompetent cells could migrate into the distant region of the vestibule and cochlea, though antigen did not spread in these region. IFN-gamma was immediately generated and reached maximum at 6 hours. IFN-gamma expression was also recognized in the vestibule and the cochlea, followed by ICAM-1 expression reached maximum at 12 hours. These results suggest that inflammatory cytokine generated in the sac stimulate ICAM-1 expression in the entire inner ear and induce the migration of immnocompetent cells into the inner ear without direct antigen stimulation. Additionally, cell proliferation occurred in the sac of this animal model. Therefore, the sac may play an important role in the inner ear immune defense as well as may cause an etilogy of inner ear immune injury.Endothelin-1 (ET-1) activity was seen in the important sites of the inner ear for water balance and the transduction of the sensory nerve. ET-1 activity was strongly affected in this animal model, suggesting an important function of ET-1 for maintaing homeostasis of the microenvironment of the inner ear.Autoimmune etiology was examined in the C57BL/6 mice employing cow inner ear tissue antigen. Preliminary results showed migration of lymphocytes and PMN predominatly in the perilymphatic region, but not in the other organs. Western blot assay using cow inner ear tissue showed several positive bands reacted with serum of patients with inner ear diseases. Further investigation is essential for an autoimmune etiology of Meniere's disease.