Hashimoto Shigehisa, Billings Peter, Harris Jeffrey P, Firestein Gary S, Keithley Elizabeth M
Division of Otolaryngology-Head and Neck Surgery, University of California, San Diego, 9500 Gilman Dr., CA 92093-0666, USA.
Audiol Neurootol. 2005 Jan-Feb;10(1):35-43. doi: 10.1159/000082306. Epub 2004 Nov 23.
Inner ear immune responses mediated by antigen-specific processes are thought to contribute to hearing loss in humans. Systemic activation of innate immunity contributes to immune responses in the central nervous system. We hypothesized that activation of innate immunity can prime the inner ear for adaptive immune responses and exacerbate disease. Mice were systemically immunized with antigen. Three weeks after initial antigen exposure, the antigen was injected intrathecally coincident with systemic injection of lipopolysaccharide (LPS), an activator of innate immunity. Responses were measured by quantifying the leukocyte infiltrate and cochlear IL-1beta expression. LPS stimulation markedly amplified the adaptive immune response to exogenous antigen in the inner ear. These data indicate that the cochlea is activated by systemic events that stimulate innate immunity and when antigen is present in the inner ear, a robust cochlear adaptive response is generated. If true in humans, this implies that priming may be an important component in the development of immune-mediated hearing loss.
由抗原特异性过程介导的内耳免疫反应被认为与人类听力损失有关。先天免疫的全身激活有助于中枢神经系统的免疫反应。我们假设先天免疫的激活可使内耳为适应性免疫反应做好准备并加剧疾病。用抗原对小鼠进行全身免疫。在初次接触抗原三周后，将抗原鞘内注射，同时全身注射脂多糖（LPS），一种先天免疫激活剂。通过量化白细胞浸润和耳蜗IL-1β表达来测量反应。LPS刺激显著增强了内耳对外源抗原的适应性免疫反应。这些数据表明，耳蜗被刺激先天免疫的全身事件激活，并且当内耳存在抗原时，会产生强烈的耳蜗适应性反应。如果在人类中也是如此，这意味着启动可能是免疫介导性听力损失发展中的一个重要因素。
