Acoustic Trauma Augments the Cochlear Immune Response to Antigen

Authors

  • Masumichi Miyao MD,

    1. Divisions of Otolaryngology–Head and Neck Surgery, University of California, San Diego, La Jolla, California, U.S.A.
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  • Gary S. Firestein MD,

    1. Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, California, U.S.A.
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  • Elizabeth M. Keithley PhD

    Corresponding author
    1. Department of Veterans Affairs, Medical Research Division, San Diego VA Medical Center, San Diego, California, U.S.A.
    • Elizabeth M. Keithley, PhD, Division of Otolaryngology–Head and Neck Surgery, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0666
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  • This work was supported by the Medical Research Service of the Department of Veterans Affairs.

    Portions of this work were presented at the Midwinter Meeting of the Association for Research in Otolaryngology, Denver, Colorado, U.S.A., February 12, 2007.

Abstract

Objectives/Hypothesis: To test whether noise-exposure, which activates a cochlear immune response with cytokine expression and infiltration of circulating leukocytes could augment the response to antigen (Ag).

Study Design: Randomized, prospective, mice.

Methods: We sensitized mice to an Ag, injected it intrathecally, and subsequently exposed the mice to noise (8–16 kHz, 90, 100, or 118 dB for 2 hours). Control mice received either noise exposure alone (100 or 118 dB), Ag challenge alone, intrathecal surgery and phosphate-buffered saline injection or no treatment. Four hours or 7 days later the mice were killed and cochlear sections were evaluated immunohistochemically for CD45, ICAM-1, and phospho-nuclear transcription factor-κB expression.

Results: Intrathecal Ag injection caused no hearing loss, but did result in a small immune response. Loud noise (118 dB) caused severe hearing loss and slight inflammation. The number of CD45-positive cells was significantly greater in the Ag plus-118 dB noise group relative to the Ag-alone group or 118 dB noise-exposure group. ICAM expression was seen in the lower part of the spiral ligament and small vessels within the normal cochlea. The amount of expression increased after Ag injection and acoustic trauma. Activated nuclear transcription factor-κB occurred in the nuclei of hair cells, supporting cells, spiral ligament fibrocytes, and neurons 4 hours after noise exposure.

Conclusions: It seems that noise exposure can activate a cochlear immune response, which in the presence of Ag, allows for greater recruitment of inflammatory cells than occurred in response to Ag alone.

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