TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo

Int J Audiol. 2013 Aug;52(8):545-52. doi: 10.3109/14992027.2013.790564. Epub 2013 Jun 20.

Abstract

Objective: Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-α inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo.

Design: After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear.

Study sample: Guinea pigs (n = 6, per group).

Results: Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-α inhibitor in contrast to a significant threshold raising in controls.

Conclusions: TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Threshold / drug effects
  • Capillaries / drug effects*
  • Capillaries / immunology
  • Capillaries / physiopathology
  • Cochlea / blood supply*
  • Disease Models, Animal
  • Etanercept
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Guinea Pigs
  • Hearing Loss, Noise-Induced / immunology
  • Hearing Loss, Noise-Induced / physiopathology
  • Hearing Loss, Noise-Induced / prevention & control*
  • Immunoglobulin G / pharmacology*
  • Male
  • Microcirculation / drug effects*
  • Receptors, Tumor Necrosis Factor
  • Regional Blood Flow / drug effects
  • Time Factors
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept