1991 Fiscal Year Final Research Report Summary
The Mechanism in the production of neutralizing autoantibodies against IL-1
| Project/Area Number |
02807207
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
医学一般
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| Research Institution | Institute of Clinical Medicine, University of Tsukuba |
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Principal Investigator |
SUZUKI Hiroshi Inst, of Clinical Medicine, Lecturer University of Tsukuba., 臨床医学系, 講師 (00179243)
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| Project Period (FY) |
1990 – 1991
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| Keywords | interleukin 1 / Anti-IL-1 autoantibody / Anti-cytokine autoantibody / Interleukin 6 |
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| Research Abstract |
In order to investigate the mechanism by which anti-IL-1alpha autoantibodies develop, we first examined immunological characteristics of the autoantibodies. The affinity of the autoantibodies was extremely high(Kd-10^<-11> l/M)and neutralizing activities of the autoantibodies were proportional to the binding activities of the autoantibodies to IL-1 alpha, suggesting that the autoantibodies recognize very restricted portions of IL-1 alpha molecules and are against IL-1 alpha itself, but not to some other molecules cross-reactive to IL-1 alpha. The fluctuations of the titers of anti-IL-1 alpha autoantibodies during clinical course of rheumatoid arthritis further suggested that the development of the autoantibodies resulted from immune response to IL-1 alpha present in synovial tissues of active rheumatoid arthritis. We have next tried to make monoclonal anti-IL-1alpha autoantibodies by fusion of a mouse-human heterohybridoma cell line to EB-virus transformed B cell lines producing anti-IL-lalpha antibodies, but have not yet succeeded in the project. During the investigation of other anti-cytokine autoantibodies, we found anti-IL-6 autoantibodies which were observed at increased frequency in patients with systemic sclerosis(about 17 %)compared with normal subjects(about 2 %). Anti-IL-6 autoantibodies have several different characteristics from anti-IL-1alpha autoantibodies. Anti-IL-6 autoantibodies are present as complex with IL-6 in vivo and showed IL-6 activity, suggesting the roles of the autoantibodies as carriers of IL-6 in vivo.
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