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The Mechanism in the production of neutralizing autoantibodies against IL-1

Research Project

Project/Area Number 02807207
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 医学一般
Research InstitutionInstitute of Clinical Medicine, University of Tsukuba

Principal Investigator

SUZUKI Hiroshi  Inst, of Clinical Medicine, Lecturer University of Tsukuba., 臨床医学系, 講師 (00179243)

Project Period (FY) 1990 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsinterleukin 1 / Anti-IL-1 autoantibody / Anti-cytokine autoantibody / Interleukin 6 / ILー1 / ILー6 / 自己抗体
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.

Report

(3 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Hiroshi Suzuki: "Demonstration of neutralizing autoantibodies against IL-1α in sera from patients with rheumatoid arthritis." Jouranal of Immunology. 145. 2140-2146 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki: "Anti-interleukin 1α autoantibodies in rheumatic diseases and in normal subjects" Clinical Experimental Immunology. 85. 407-412 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki: "Molecular biology of cytokine effects on vascular endothelial cells" International Review of Experimental Pathology. 32. 95-148 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 鈴木 博史: "抗サイトカイン自己抗体と炎症" 炎症. 11. 415-420 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 鈴木 博史: "内皮細胞とサイトカイン内皮細胞の活性化を中心として" 現代医療. 23. 1800-1804 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroyuki Takemura: "Anti-interleukin-6 auto antibodies in rheumatic diseases.Significant increase of positive sera in patients with cystemic sclerosis" Arthritis and Rheumatism.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki et al.: "Demonstration of neutralizing auto-antibodies against IL-1 alpha in sera from patients with rheumatoid arthritis." J. Immunol.145. 2140-2146 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki et al.: "Anti-interleukin 1alpha autoantibodies in rheumatic diseases and in normal subjects." Clin. exp. Immunol.85. 407-412 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki et al.: "Molecular biology of cytokine effects on vascular endothelial cells." Int. Review of Exp. Pathology. 32. 95-148 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki: "Anti-cytokine autoantibody and inflammation (in Japanese)" Enshou. 11. 415-420 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroshi Suzuki: "Endothelial cells and cytokines. Activation of endothelial cells (in Japanese)" Gendaiiryou. 23. 1800-1804 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Hiroyuki Takemura: "Anti-interleukin-6 autoantibodies in rheumatic diseases. Significant increase of positive sera in patients with systemic sclerosis." Arthritis Rheum.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takemura Hiroyuki: "Antiーinterleukinー6 autoantibodies in Rheumatic disanses.Significant increase of pos:tive sera in patitients with systemle sclensis" Arthritis Rheum.

    • Related Report
      1991 Annual Research Report
  • [Publications] Suzuki Hiroshi: "AntiーILー1α autoantibodies in patients with rheumatic diseases and in healtly subjects" Clinical Experimental Immunology. 85. 407-412 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suzuki Hiroshi: "Molecular biology of cytokine ettects on vascular endothelial cells" International Review of Experimental Pachology. 32. 95-148 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 鈴木 博史: "抗サイトカイン自己抗体と炎症" 炎症. 11. 415-420 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 鈴木 博史: "内皮細胞とサイトカイン 内皮細胞の活性化を中心として" 現代医療. 23. 3111-3114 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 鈴木 博史: "サイトカインに対する自己抗体の意義" 臨床免疫. 23. 1800-1804 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Hiroshi Suzuki: "Demonstration of neutralizing autoantiboclies against ILー1α in sera from patients with rheumatoid archritis" Journal of Immunology. 145. 2140-2146 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroshi Suzuki: "Antiーinterleukin 1α autoantiboclies in rheumatic diseases and in normal subjects" Clinical Experimental Immunology.

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroyuki Takemura: "Increased frequency of antiーILー6 autoantiboclies in patients with systemic sclerosis" Arthritis and Rheumatism.

    • Related Report
      1990 Annual Research Report
  • [Publications] 鈴木 博史: "リウマチ性疾患と抗インタ-ロイキン1自己抗体" リウマチ科. 3. 199-204 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiroshi Suzuki: "Molecular biology of cytokine effects on vascular endothelial cells.International Review of Experimental Pathology vol.32(印刷中)" Academic Press, (1991)

    • Related Report
      1990 Annual Research Report

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Published: 1990-04-01   Modified: 2016-04-21  

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