Immunologic responses in experimental cytomegalovirus labyrinthitis.

To better understand the pathogenesis of cytomegalovirus labyrinthitis, a guinea pig model was created. Following inoculation at several sites (cardiac, perilymph, and endolymphatic sac) in both seronegative and seropositive animals, the immunologic, histologic, and electrophysiologic responses were measured. Seronegative animals uniformly showed progressive hearing loss with marked inflammation and degeneration of neural elements. In animals inoculated into the endolymphatic sac, an associated endolymphatic hydrops developed in addition to deafness. Seropositivity protected the hearing, but endolymphatic sac inoculations resulted in mild hydrops due to local inflammation that was devoid of evidence of viral replication. The question of whether hearing loss was attributable to local inflammatory responses rather than the cytopathic effects of the virus was then examined. To test this hypothesis, animals were immunosuppressed with cyclophosphamide prior to intracochlear inoculation of cytomegalovirus. The immunosuppressed animals showed significantly better hearing than the controls, and this correlated directly with the degree of cellular infiltration of the scala tympani. These studies confirm the importance of host immune responses in the pathogenesis of hearing loss due to cytomegalovirus.