Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea

Kenichiro Wakabayashi, Masato Fujioka, Sho Kanzaki, Hirotaka James Okano, Shinsuke Shibata, Daisuke Yamashita, Masatsugu Masuda, Masahiko Mihara, Yoshiyuki Ohsugi, Kaoru Ogawa, Hideyuki Okano

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)345-352
Number of pages8
JournalNeuroscience Research
Volume66
Issue number4
DOIs
Publication statusPublished - 2010 Apr 1

Keywords

  • Cytokine
  • Inflammation
  • Inner ear
  • Interleukin-6
  • Macrophage
  • Noise exposure
  • Spiral ganglion

ASJC Scopus subject areas

  • Neuroscience(all)

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