Blockage of immune-mediated inner ear damage by etanercept

Hypothesis: Etanercept will be able to reduce the inflammation and hearing loss associated with experimentally induced labyrinthitis. Background: Inner ear immune responses cause hearing loss that may be reversible with pharmacologic treatment. Etanercept, tumor necrosis factor receptor blocker, was investigated in a guinea pig model of immune-mediated hearing loss. Sterile labyrinthitis was created by injection of keyhole limpet hemocyanin into the inner ear after systemic sensitization to keyhole limpet hemocyanin with adjuvant. Labyrinthitis involves infiltration of inflammatory cells and hearing loss detectable 3 to 5 days after challenge with keyhole limpet hemocyanin. Methods: Etanercept was administered either systemically (2.5 mg) 30 minutes before intracochlear challenge with keyhole limpet hemocyanin, with a second intraperitoneal dose (2.5 mg) 3 days later or locally by long-term infusion into the scala tympani with an osmotic pump (5.0 mug/h for 7 days). Auditory evoked brainstem response thresholds were measured before and after treatment to determine hearing loss. Cochleas were evaluated for the amount of inflammation. Results: Hearing loss in the untreated systemic group averaged 71 +/- 21 dB versus 37 +/- 32 dB in the etanercept-treated animals (t test, P < 0.001). There was also less inflammation in the cochleas from etanercept-treated animals (t test, P < 0.01). Hearing loss with local administration of etanercept was 59 31 dB in the nontreated ears and 18 +/- 8 dB in the treated ears (t test P < 0.02). Inflammation was also less (t test, P < 0.01). Etanercept was not ototoxic. Conclusion: Prompt intervention with the anti-inflammatory drug etanercept significantly reduces inflammation sufficient for substantive hearing preservation.