Transforming growth factor β expression during an inner ear immune response

Objectives: The involvement of transforming growth factor beta (TGF-beta), a strong mediator of fibrogenesis, during cochlear immune responses was investigated. Methods: An inner ear adaptive immune response to antigen was created in mice that were painlessly sacrificed 3 to 48 0 hours and 7 days after initiation of the immune response. The cochleas were assayed by immunocytochemistry for TGF-beta and latency-associated peptide (LAP). Results: We found LAP expressed in normal cochleas and the endolymphatic sac, in the small round cells in the cochlear scalae and the mesothelial cells under the basilar membrane, and in the endolymphatic sac perisaccular area. We found TGF-beta expressed in infiltrated, inflammatory cells in the scalae and the endolymphatic sac lumen 3 hours after cochlear antigen challenge. At this time, LAP immunoreactivity was decreased. This rapid shift in immunoreactivity provides evidence for activation of TGF-beta during an immune response. This reversal of expression persisted for 48 hours, but conditions reverted to normal after 7 days. Surgical controls did not show TGF-beta expression. Conclusions: We conclude that TGF-beta activation occurs in the early phase of a cochlear adaptive immune response and is down-regulated as the response resolves. This finding suggests that the process of cochlear fibrosis starts early and that proper treatment could prevent cochlear fibrosis.