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1996 Fiscal Year Final Research Report Summary

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
Keywordsinflammation / cytokine / TNF / IL-8 / IL-1 / 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.

  • Research Products

    (22 results)

All Other

All Publications (22 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 1999-03-09  

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