Recently there has been a growing interest in the possibility that some forms of progressive sensorineural hearing loss may have immunological bases and may actually be improved following the institution of immunosuppressive agents. In conjunction with these observations, the inner ear has been shown experimentally to be immunoresponsive through the characterization of humoral immune responses within the inner ear as a result of antigen challenge. The major objectives in this grant proposal are to better understand how immunological responses within the inner ear are generated, the origin of these responses, their effect on cochlear function and their possible relationship to human conditions. Specifically, this project will investigate the fate of inner ear antigen challenge, the site of antigen processing and antibody production, the antibody classes evolving within the inner ear, the role of the endolymphatic sac in inner ear immune responses, the temporal effects of immunity on cochlear function, the mechanisms responsible for immune mediated inner ear injury, the role of complement in these responses, whether an animal model of autoimmune sensorineural hearing loss can be created and whether patients with Meniere's disease can be shown to have an immunological basis to their disease. These studies will involve well characterized animal models of inner ear immunity in which inner ear immune responses can be measured by a sensitive enzyme immunoassay, lymphocyte blastogenesis assays, immunohistochemical localization studies, adoptive transfer studies, electrophysiological monitoring and cochlear metabolism and blood flow analyses. Additionally, patients with Meniere's disease will undergo in vitro assays of lymphocyte blastogenesis in order to assess whether cellular immune mechanisms are at play in this disorder. Serum from these patients will also be screened for antibodies to the inner ear by an enzyme immunoassay system. These studies should clarify the relationship of the inner ear to host and local immune responses and determine whether this interaction is protective or possibly deleterious to normal physiological function and thereby result in disease states.
| Darrow, D H; Keithley, E M; Harris, J P (1992) Effects of bacterial endotoxin applied to the guinea pig cochlea. Laryngoscope 102:683-8 |
| Krekorian, T D; Keithley, E M; Fierer, J et al. (1991) Type B Haemophilus influenzae-induced otitis media in the mouse. Laryngoscope 101:648-56 |
| Krekorian, T D; Keithley, E M; Takahashi, M et al. (1990) Endotoxin-induced otitis media with effusion in the mouse. Immunohistochemical analysis. Acta Otolaryngol 109:288-99 |
| Keithley, E M; Krekorian, T D; Sharp, P A et al. (1990) Comparison of immune-mediated models of acute and chronic otitis media. Eur Arch Otorhinolaryngol 247:247-51 |
| Harris, J P (1989) Autoimmunity of the inner ear. Am J Otol 10:193-5 |
| Gloddek, B; Harris, J P (1989) Role of lymphokines in the immune response of the inner ear. Acta Otolaryngol 108:68-75 |
| Berchtold, P; Harris, J P; Tani, P et al. (1989) Autoantibodies to platelet glycoproteins in patients with disease-related immune thrombocytopenia. Br J Haematol 73:365-8 |
| Tomiyama, S; Keithley, E M; Harris, J P (1989) Antigen-specific immune response in the inner ear. Ann Otol Rhinol Laryngol 98:447-50 |
| Takahashi, M; Peppard, J; Harris, J P (1989) Immunohistochemical study of murine middle ear and Eustachian tube. Acta Otolaryngol 107:97-103 |
| Tomiyama, S; Harris, J P (1989) Elevation of inner ear antibody levels following direct antigen challenge of the endolymphatic sac. Acta Otolaryngol 107:202-9 |
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