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Determination of cytokines involved in initiation of acute inflammation.

Research Project

Project/Area Number 07457060
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionKumamoto University School of Medicine

Principal Investigator

YOSHINAGA Masaru  (First Department of Pathology) Kumamoto University School of Medicine, Professor, 医学部, 教授 (90040196)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥6,000,000 (Direct Cost: ¥6,000,000)
Keywordsinflammation / cytokine / TNF / IL-8 / IL-1 / IL-1ra / TNFα / IL-lβ / IL-lra / IL-1β / IL-1ra
Research Abstract

To know the cytokines involved in the development of inflammation. We developed a subtraction gene library of rabbit and detected several candidate cytokines which are specifically expressed during the course of inflammation, i.e.TNFalpha), IL-8, IL-1beta and IL-1ra. Then, we made recombinants and antibodies of these gene products and investigated the significance of these cytokines in the pathogenesis of LPS-induced acute inflammation in rabbits.
We conclude the followings :
1. TNFalpha and IL-8 were produced during the initial stage (within 2 hrs). The production of these cytokines were mutually independent, namely inhibition of one of these did not suppressed the production of the other. The production was not reduced by depletion of neutrophils. Immunostaining revealed that resident cells were positive for these two cytokines, but not neutrophils.
2. IL-1beta was produced during a later stage (peaked at 6 hrs). Production of IL-1beta was induced by both TNFalpha and IL-8 ; namely, inhibition of the two cytokines resulted in reduced production of IL-1beta. Recombinant TNFalpha or IL-8 induced the strong production of IL-1beta.
3. IL-1 ra was produced by infiltrated neutrophils and macrophages and suppressed by inhibition of TNFalpha and IL-8. Recombinant IL-1ra suppressed the infiltration of neutrophils. Inhibition of IL-1ra produced enhanced neutrophil infiltration and tissue destruction.
4. Inhibition of TNFalpha or IL-8 resulted in a partial inhibition of neutrophil infiltration at an early stage (2 hrs) of inflammation, but not those in a later stage (9 hrs).
5. Inhibition of IL-1 resulted in reduced neutrophil infiltration at the later stage of inflammation. Then, we reached a conclusion that both TNFalpha and IL-8 act as initiation of inflammation and IL-1beta play a role in the amplification of acute inflammation.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Akihiro Matsukawa: "Analysis of the inflammatory cytokine network among TNFα,IL-1β,IL-1 receptor antagonist and IL-8 in LPS-induced rabbit arthritis." Laboratory Investigation. (印刷中). (1977)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihiro Matsukawa: "IL-1 receptor antagonist in tissues from healthy rabbits and in endotoxemia-related changes. IL-1 receptor antagonist has the potential to regulate over-actions of IL-1 in health and disease." Cytokine. (印刷中). (1977)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sumitaka Imamura: "Involvement of tumor necrosis factor-α,interleukin-1β,interleukin-8,and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction." Pathology International. 47. 16-24 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Makoto Kimura: "Blocking of TNF-α and IL-1 inhibits leukocyte infiltration at early,but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits." Clinical Immunology and Immunopathology. 82. 18-25 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jim Apostolopoulos: "Interleukin-1 antagonist : Characterization of its gene expression in rabbit tissues and large-scale expression in eucaryotic cells using a baculovirus expression system." Journal of Immunological Methods. 199. 27-35 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takumi Fukumoto: "Administration of neutralizing antibody against rabbit IL-1 receptor antagonist exacerbates lipopolysaccharide-induced arthritis in rabbits." Inflammation Research. 45. 479-485 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fumiharu Yanagi: "Cytokine generation in rabbits during ECLA with a mini hollow fiber lung." Artificial Organs. 20. 209-217 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Y.A.Dlsayed: "Expression of tissue factor and interleukin-1β in a novel rabbit model of disseminated intravascular coagulation induced by carrageenan and lipopolysaccharide." Pathobiology. 63. 328-340 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ki-ichi Kakimoto: "Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis." Cellural Immunology. 165. 26-32 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihiro Matsukawa: "Neutrophil accumulation and activation by homologous IL-8 in rabbits." Journal of Immunology. 154. 5418-5425 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Sunao Edamitsu: "Role of TNFα,IL-7 and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy." Clinical Immunology and Immunopathology. 75. 68-74 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsukawa A.et al.: "Analysis of the inflammatory cytokine network among TNFalpha, IL-1beta, IL-1 receptor antagonist and IL-8 in LPS-induced rabbit arthritis." Laboratory Investigation. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsukawa A., et al.: "IL-1 receptor antagonist in tissues from healthy rabbits and in endotoxemia-related changes. IL-1 receptor antagonist has the potential to regulate overactions of IL-1 in health and disease." Cytokine. (in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Imamura S., et al.: "Involvement of tumor necrosis factor-alpha, interleukin-1beta, interleukin-8, and interleukin-1 receptor antagonist in acute lung injury caused by local Shwartzman reaction." Pathology International. 47. 16-24 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kimura M., et al.: "Blocking of TNF-alpha and IL-1 inhibits leukocyte infiltration at early, but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits." Clinical Immunology and Immunopathology. 82. 18-25 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Apostolopoulos J., et al.: "Interleukin-1 antagonist : Characterization of its gene expression in rabbit tissues and large-scale expression in eucaryotic cells using a baculovirus expression system." Journal of Immunological Methods. 199. 27-35 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fukumoto T., et al.: "Administration of neutralizing antibody against rabbit IL-1 receptor antagonist exacerbates lipopolysaccharide-induced arthritis in rabbits." Inflammation Research. 45. 479-485 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yanagi F., et al.: "Cytokine generation in rabbits during ECLA with a mini hollow fiber lung." Artificial Organs. 20. 209-217 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Dlsayd Y.A., et al.: "Expression of tissue factor and interleukin-1beta in a novel rabbit model of disseminated intravascular coagulation induced by carrageenan and lipopolysaccharide." Pathobiology. 63. 328-340 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kakimoto K., et al.: "Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis." Cellular Immunology. 165. 26-32 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Matsukawa A., et al.: "Neutrophil accumulation and activation by homologous IL-8 in rabbits." Journal of Immunology. 154. 5418-5425 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Edamitsu S., et al.: "Role of TNFalpha, IL-1 and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy." Clinical Immunology and Immunopathology. 75. 68-74 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihiro Matsukawa: "Analysis of the inflammatory cytokine network among TNFα,IL-lβ,IL-l receptor antagonist and IL-8 in LPS-induced rabbit arthritis." Laboratory Investigation. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akihiro Matsukawa: "IL-l receptor antagonist in tissues from healthy rabbits and in endotoxemia-related changes.IL-l receptor antagonist has the potential to regulate over-actions of IL-l in health and disease." Cytokine. (印刷中). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sumitaka Imamura: "Involvement of tumor necrosis factor-α,interleukin-lβ,interleukin-8,and interleukin-l receptor antagonist in acute lung injury caused by local Shwartzman reaction." Pathology International,. 47. 16-24 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Makoto Kimura: "Blocking of TNF-α and IL-l inhibits leukocyte infiltration at early, but not at late stage of Staphylococcus aureus-induced arthritis and concomitant cartilage destruction in rabbits." Clinical Immunology and Immunopathology. 82. 18-25 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Takumi Fukumoto: "Administration of neutralizing antibody against rabbit IL-l receptor antagonist exacerbates lipopolysaccharide-induced arthritis in rabbits." Inflammation Research. 45. 479-485 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fumiharu Yanagi: "Cytokine generation in rabbits during ECLA with a mini hollow fiber lung." Artificial Organs,. 20. 209-217 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Yoshinaga M: "Neutrophil accumulation and activation by homologous IL-8 in rabbits." J.Immunology. 154. 5418-5425 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshinaga M: "Role of TNFα,IL-1 and IL-1ra in the mediation of leukocyte infiltration and increased vascular permeability in rabbits with LPS-induced pleurisy." Clin.Immunol.Immunopathol.75. 68-74 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshinaga M: "Suppressive effect of a neutrophil elastase inhibitor on the development of collagen-induced arthritis." Cell.Immunology. 165. 26-32 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshinaga M: "Assessment of a long-term extracorporeal lung assist without blood transfusion in rabbits ; with special reference to production of cytokines." Artificial Organ. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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