Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation.
OBJECTIVE
The inner ear rapidly mounts an immune response that can lead to cochlear degeneration and permanent hearing loss. Identification of proinflammatory cytokine expression during the initiation of the response should lead to rational therapeutic strategies that block the response, reducing damaging sequelae.


METHODS
A cochlear immune response to keyhole limpet hemocyanin (KLH) injected into the inner ear or subarachnoid space of sensitized animals was created. Etanercept was administered to a group of animals to blunt the immune response.


METHODS
Cochleae were immunoassayed for expression of interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 and evaluated for the amount of cochlear-infiltrated cells.


RESULTS
Tumor necrosis factor-alpha and interleukin-1beta were expressed by infiltrated cells shortly after KLH injection. Tumor necrosis factor-alpha was expressed whether the antigen was introduced with or without surgical trauma. Interleukin-1beta was also expressed by the cochlear fibrocytes during the immune response and in surgical control animals, but not after intrathecal injection of antigen. Interleukin-6 expression was minimal during the response. Based on this observation, animals were treated with systemic injection of Etanercept, which reduced cochlear infiltrating cell number and cochlear fibrosis.


CONCLUSIONS
Interleukin-1beta expression is a general cochlear response to trauma, whereas tumor necrosis factor-alpha expression in the infiltrated immunocompetent cells is the cytokine that induces amplification of the response that leads to cochlear disease.
D000818:Animals; D003051:Cochlea / Q000276:immunology* / Q000378:metabolism; D000068800:Etanercept; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D006433:Hemocyanins; D000068800:Etanercept