High dose combination pertussis toxin induces autoimmune inner ear disease in Sprague-Dawley rats

• Published in: Acta oto-laryngologica 2011-07, Vol.131 (7), p.692-700
• Main Authors: Kong, Wei-Jia, Wang, Deng-Yuan, Huang, Xiang, Ding, Guo-Feng
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune Diseases - chemically induced; Autoimmune Diseases - immunology; Autoimmune Diseases - physiopathology; Bacterial diseases; Biological and medical sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Ear, Inner - drug effects; Ear, Inner - pathology; Ent and stomatologic bacterial diseases; Female; hearing loss; Human bacterial diseases; Immunohistochemistry; Infectious diseases; Injections, Intraperitoneal; inner ear; Labyrinth Diseases - chemically induced; Labyrinth Diseases - immunology; Labyrinth Diseases - pathology; Labyrinth membrane; Male; Medical sciences; Non tumoral diseases; Otorhinolaryngology. Stomatology; Pertussis Toxin - administration & dosage; Pertussis Toxin - toxicity; Rats; Rats, Sprague-Dawley
• ISSN: 0001-6489; 1651-2251
• DOI: 10.3109/00016489.2011.552525

Abstract Conclusion: A better animal model of autoimmune inner ear disease (AIED) in Sprague-Dawley rats has been developed by combination with high dose of pertussis toxin. This study also indicated that inner ear-specific antigens can be involved in autoimmune reactions. Cell-mediated immune injury can play an important role in the induction of AIED, at least in the earlier stage. Objectives: The purpose of this study was to develop a more suitable rat model that demonstrated closer resemblance to the pathophysiological process in AIED. Methods: Ninety-six female Sprague-Dawley rats were divided into four groups. They were subcutaneously immunized with crude inner ear antigen/complete Freund's adjuvant (CIEAg/CFA), or intraperitoneal injection of 500 ng pertussis toxin (PT), or injection of CIEAg/CFA+PT, or phosphate-buffered saline (PBS) alone. The auditory function, histopathology of the inner ear, and autoantibodies were examined. Results: Significant differences in the time course of auditory brainstem response (ABR) threshold and mean score of cellular infiltration were demonstrated in the CIEAg/CFA+PT group of animals. Missing hair cells, degeneration of the spiral ganglion cells, endolymphatic hydrops, and autoantibodies were all noted after immunization. There were no significant differences in ABR threshold or histopathology in any other group of animals.