Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea.
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 6h 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 4kHz 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.
Wakabayashi
Kenichiro
K
Department of Otolaryngology, Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinju-ku, Tokyo 160-8582, Japan.
Fujioka
Masato
M
Kanzaki
Sho
S
Okano
Hirotaka James
HJ
Shibata
Shinsuke
S
Yamashita
Daisuke
D
Masuda
Masatsugu
M
Mihara
Masahiko
M
Ohsugi
Yoshiyuki
Y
Ogawa
Kaoru
K
Okano
Hideyuki
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015834:Cochlear Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000503:physiopathology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000502:physiology; D007762:Labyrinthitis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009622:Noise / Q000009:adverse effects*; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors