Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation.

Abstract

OBJECTIVES/HYPOTHESIS:

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.

STUDY DESIGN:

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.

CONCLUSION:

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.

• Authors: Hitoshi Satoh, Gary S Firestein, Peter B Billings, Jeffrey P Harris, Elizabeth M Keithley
• Journal: The Laryngoscope (Laryngoscope) Vol. 112 Issue 9 Pg. 1627-34 (Sep 2002) ISSN: 0023-852X [Print] United States
• PMID: 12352677 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Immunoglobulin G
• Immunosuppressive Agents
• Interleukin-1
• Interleukin-6
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Hemocyanins
• Etanercept

Topics

• Animals
• Cochlea (immunology, metabolism)
• Etanercept
• Female
• Hemocyanins (immunology)
• Immunoglobulin G (pharmacology)
• Immunosuppressive Agents (pharmacology)
• Interleukin-1 (metabolism)
• Interleukin-6 (metabolism)
• Mice
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha (immunology)