2000 Fiscal Year Final Research Report Summary
STUDY OF PATHOGENESIS IN AUTOIMMUNE INUJRY OF THE INNER EAR
| Project/Area Number |
10671621
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | NIPPON MEDICAL SCHOOL |
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Principal Investigator |
TOMIYAMA Shunichi NIPPON MEDICAL SHOOL, DEPARTMENT OF OTOLARYNGOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (00094665)
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| Project Period (FY) |
1998 – 2000
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| Keywords | INNER EAR / AUTOIMMUNE / immunohistchemistry / CD4 / IL-2 / IFN-γ / western blot / autoantibody |
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| Research Abstract |
This study was designed to establish an experimental autoimmune labyrinthitis model in inbred mouse, which could exhibit high reproducibility and be adopted for precise immunological analysis. Following pretreatment with cyclophosphamide and primary sensitization with inner ear antigen (IEA) in FCA, many inflammatory cells transiently infiltrated into the whole area of the inner ear. This reaction occurred in all animals and peaked on day 12. This labyrinthitis was passively transferred by sensitized lymphocytes. Many CD4+ cells with IFN-γ+ and IL-2+ infiltrated mainly the endolymphatic sac as early as day 4, gradually into the whole area of the inner ear and persisted until day 35. On the other hand, very few CD8+ cells infiltrated on day 10 and rapidly disappeared. These results suggested that primary sensitization induce cellular autoimmune reaction in the inner ear mediated by helper T1 (Th1 ) lymphocytes. Repeated sensitization with IEA produced autoantibody to the inner ear. Western blot assay demonstrated three different serum antibodies, which reacted to 45, 66, 200 KD of the bovine inner ear antigen. IgG deposited mainly in the vessels of the stria vascularis and bone labyrinthine. Repeated sensitization with IEA stimulates humor mediated autoimmune reaction and autoantibody may alter morbid state of chronic stage of autoirmmune labyrinthitis. Immune reaction in the endolymphatic sac generates immune injury by nitric oxide, apoptotic degeneration, as well as sympathetic labyrinthitis.
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