Effects of Cyclophosphamide on the Pathogenesis of Cytomegalovirus-Induced Labyrinthitis

Abstract

Cyclophosphamide was used in this study to define the contribution of the inflammatory response relative to direct cytopathic effects of guinea pig cytomegalovirus (GPCMV) in inducing sensorineural hearing loss in the guinea pig. The eighth nerve compound action potential (CAP) threshold on day 7 after inoculation of GPCMV into the scala tympani was an average of 35 dB greater for control animals than for those that were immunosuppressed with daily intraperitoneal injections of cyclophosphamide (20 mg/kg body weight). The amount of GPCMV antigen in the cochlea, detected immunohistochemically, did not correlate with the CAP threshold. However, the greater the inflammatory response to GPCMV in the cochlea, the higher the CAP threshold and thus the greater the hearing loss. This study demonstrates that the inflammatory response to GPCMV may be more important than direct cytopathic effects of the virus in producing sensorineural hearing loss in GPCMV-induced labyrinthitis.