Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea
Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea
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DOI：
10.1016/j.neures.2009.12.008
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发表时间：
2010-04-01
影响因子：
2.9
通讯作者：
Okano, Hideyuki
中科院分区：
文献类型：
--
作者：
Wakabayashi, Kenichiro;Fujioka, Masato;Okano, Hideyuki
听力障碍可能是造成严重社会经济不利的原因。最近的研究表明，内耳中的炎症反应与各种损伤性疾病（包括噪声引起的听力损失）同时发生。我们报道了促炎细胞因子白细胞介素-6（IL-6）诱导耳蜗噪声暴露后6小时，但这仍然是模糊的病理生理意义。为了解决这个问题，我们研究了使用抗IL-6受体抗体（MR 16 - 1）抑制IL-6的效果。在用MR 16 -1处理的噪声暴露小鼠中注意到通过听觉脑干反应（ABR）测量的4 kHz下的听力改善。组织学分析显示，在MR 16 -1处理组中螺旋神经节神经元的减少得到改善，而在Corti器官中没有观察到显著变化。免疫组化结果显示，与对照组相比，MR 16 - 1处理后耳蜗螺旋神经节内活化的巨噬细胞数量明显减少，提示MR 16 -1对噪声损伤耳蜗具有功能和病理保护作用，其机制可能与抑制神经元丢失和减轻炎症反应有关。包括IL-6阻断在内的抗炎性细胞因子治疗将是治疗急性感觉神经性耳聋的一种可行的新策略。(C)2009年爱思唯尔爱尔兰有限公司和日本神经科学学会。All rights reserved.
Hearing impairment can be the cause of serious socio-economic disadvantages. Recent studies have shown inflammatory responses in the inner ear co-occur with various damaging conditions including noise-induced hearing loss. We reported pro-inflammatory cytokine interleukin-6 (IL-6) was induced in the cochlea 6 h after noise exposure, but the pathophysiological implications of this are still obscure. To address this issue, we investigated the effects of IL-6 inhibition using the anti-IL-6 receptor antibody (MR16-1).Noise-exposed mice were treated with MR16-1 and evaluated. Improved hearing at 4 kHz as measured by auditory brainstem response (ABR) was noted in noise-exposed mice treated with MR16-1. Histological analysis revealed the decrease in spiral ganglion neurons was ameliorated in the MR16-1-treated group, while no significant change was observed in the organ of Corti. Immunohistochemistry for Iba1 and CD45 demonstrated a remarkable reduction of activated cochlear macrophages in spiral ganglions compared to the control group when treated with MR16-1.Thus, MR16-1 had protective effects both functionally and pathologically for the noise-damaged cochlea primarily due to suppression of neuronal loss and presumably through alleviation of inflammatory responses. Anti-inflammatory cytokine therapy including IL-6 blockade would be a feasible novel therapeutic strategy for acute sensory neural hearing loss. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.