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動物をモデルとした川崎病病因の免疫学的・病理学的解析

Research Project

Project/Area Number 01570548
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTeikyo University

Principal Investigator

YOSHINO Kazuya  Teikyo University, Faculty of Economics, Professor, 経済学部, 教授 (70091064)

Co-Investigator(Kenkyū-buntansha) KAWA Yohko  Teikyo University School of Medicine, Department of Dermatology, Assistant profe, 医学部, 助手 (10082273)
SUZUKI Keiji  Gunma University, College of Medical Care and Technology, Department of Patholo, 医療技術短期大学, 教授 (40008313)
OKITSU Shoko (NEGISHI Sh)  Teikyo University School of Medicine, Department of Pediatrics, Assistant profes, 医学部, 助手 (10082215)
阿部 由明  帝京大学, 医学部, 教授 (20089296)
古澤 修一  帝京大学, 医学部, 助手 (80130037)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
KeywordsKawasaki Disease / Interleukin 1 / Tumor necrosis factor alpha / Interleukin 6 / Lactobacillus casei / C3H / HeJ mice / animal model / cardiac involvement / インタ-リュウキン6 / Lactobacilus casei / HeT マウス / 心・血管疾 / 冠状動脈炎 / Kawasaki disease / IL-1 / TNF
Research Abstract

The ability of cell wall extract separated from Lactobacillus casei(LCWE)to stimulate peritoneal macrophages(PMC)of BALB/C and C3H/Hej mice, which produced the inflammatory cytokines such as IL-1, TNFalpha and IL-6 was evaluated. The measurement of cytokines in the MPC-cultured supernatants was assayed by the proliferative activity of thymocytes from C3H/Hej mice for IL-1 and of hybridoma B3BI cells for IL-6. TNFalpha was measured by the cytotoxic activity to L929 cells and by the enzyme-linked immunosorbent assay using polyclonal and monoclonal anti-murine TNFalpha antibodies.
In comparison with LPS, LCWE induced the production of IL-1 and TNFalpha in higher titers, and similar level of IL-6 production in BALB/C mice. In C3H/flej mice LCWE induced the three kinds of cytokine production in low level or not at all. The study of IL-1beta and TNFalpha MRNA expression of MPCs stimulated with LCWE supported the results of the level and time-kinetics of produced cytokines.
The induction of mur … More ine heart damages was performed by an injection of LCWE into the peritoneal cavity using a modified method reported by Lehman et al(1988). Surprisingly, only 48 hours after the treatment of LCWE(0.02 mg/g of body weight cardiac involvement, such as angitis (endocarditis, coronary arteritis and pericarditis were found. in both BALB/c and C3H/Hej mice. The overall frequency of cardiac damages was 69 %(9/13)and 57 %(5/14)in BALB/C and C3H/Hej mice respectively 48 hours later, whereas it was 28 %(7/25)and 8%(2/25)respectively at the fourth week. The histopathological pictures by HEstaining revealed marked cell infiltration in cardiac tissure, especially by macrophges and neutrophils. Moreover, . it was demonstrated that large and small cardiac arteries with inflammation were strongly stained by antibodies to cytokines such as IL-1, TNFalpha and IL-6 in the, ABC method.
The above results suggested that LCWE was a powerful in vivo and in vitro activators of macrophages and other cells which produced inflammatory cytokines, which caused murine cardiac involvement. It is thought that LCWE injecxted BALB/C mice would be good animal models for studying the hathogenesis of Kawasaki disease in man. Less

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 吉野 加津哉: "病変とマクロファ-ジー川崎病" 臨床免疫. 21. 672-686 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 吉野 加津哉: "リュウマチおよび結合組織:リュウマチ熱,リュウマチ性心病変とマクロファ-ジ" 小児科診療. 52. 257-260 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Abe,Y.: "Detection of serum antibody by the antimitogen assay against streptococcal erythrogenic toxins.Age distribution inchidren and the relation to kawasaki disease." Pediatric Res.27. 11-15 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 吉野 加津哉: "白血球と血管炎ー催炎因子を中心にしてー" 小児医学. 23. 19-41 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 沖津 祥子: "川崎病患児血清中の抗サイトカイン抗体" Progress in Medicine. 11. 57-59 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okitsu-Negishi,S.: "Suppressive effect of intravenous immunoglobulins on the activity of interleukin 1" Immunologic Res.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Abe, Y., Nakano, Y., Nakahara, T., Kamezawa, Y., Kato, I., Ushijima, H., Yoshino, K., Ito, S., Noma, S., Okitsu, S., Tajima, M.: "Detection of serum antibody by the antimitogen assay Against streptococcal erythrogenic toxins. Agedistibution in children and the relation to Kawasaki disease." Pediatric RES.27. 11-15 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Okitsu-Negishi, S., Furusawa, S., Kawa, Y., Hashira, S. Ito, S., Hiruma, F., Mizuguchi, M., Yoshino, K., Abe, T.: "Suppressive effect of intravenous immunoglobulins on the activity of interleukin 1." Immunol. Res.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 渡辺 克也: "小児全身性エリテマト-デス(SLE)に合併した稀な消化器病変の2例" 小児科診療. 44. 153-158 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉野 加津哉: "小児の全身性エリテマト-デス(SLE)ー最近の進歩基礎的研究の進歩:SLEの遺伝的背景" 小児内科. 23. 473-480 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] OkitsuーNegishi,S.: "Suppressive effect of intravenous immunoglabulins on the activity of interleukin 1" Immunologic Res.in bress.

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉野 加津哉: "免疫学的局面からみた若年性関節リウマチの病因" 小児内科.

    • Related Report
      1991 Annual Research Report
  • [Publications] 吉野 加津哉: "白血球と血管炎" 小児医学. 23. 19-41 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉野 加津哉: "感染症とインタ-ロイキンー1(ILー1),TNF" Current Concepts in Infectious Diseases. 9. 12-15 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 沖津 祥子: "川崎病患児血清中の抗サイトカイン抗体" Progress in Medicine. 11. 57-59 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] 吉野 加津哉: "川崎病" 臨床免疫. 21. 673-686 (1989)

    • Related Report
      1990 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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