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1996 Fiscal Year Final Research Report Summary

Analysis of hypothalamic-pituitary-adrenal axis dysfunction in rheumatoid arthritis

Research Project

Project/Area Number 07670536
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SANO Hajime  Kyoto Prefectural University of Medicine First Department of Internal Medicine Assistant Professor, 医学部, 助手 (00196304)

Project Period (FY) 1995 – 1996
KeywordsRheumatoid arthritis / Corticotropin-releasing hormone / beta-endorphin / neuropeptides / Synovium / Alzet pump / Adjuvant arthritis / Hypothalamic-pituitary-adrenal axis dysfunction
Research Abstract

We examined hypothalamic-pituitary-adrenal (HPA) axis dysfunction in the pathogenesis of rheumatoid arthritis in human and adjuvant or SCW arthritis in rats.
1) CRH and beta-endorphin were expressed in RA synovia (lining cell layr, inflammatory mononuclear cells, fibroblast-like cells, blood vessels) using immunohistochemistry, PCR method and in situ hybridization. 2) The expression of CRH and beta-endorphin in RA synovia was significantly increased compared to osteoarthritis (OA) synovia. 3) CRH mRNA was also expressed in lining cell layr, inflammatory mononuclear cells, fibroblast-like cells and blood vessels of RA patients 4) CRH and beta-endorphin were also expressed in synovium, cartilage and skin in model rats for RA (SCW or adjuvant arthritis). 5) Glucocorticoid suppressed SCW and adjuvant arthritis in Lewis rats as well as CRH and beta-endorphin expression. 6) Injection of anti-CRH antibody or anti-beta-endorphin suppressed arthritis scores in adjuvant-induced Lewis rats (40-50%). 7) Anti-CRH antibody or anti-beta-endorphin suppressed CRH and beta-endorphin in synovium and cartilage.
These data suggest ; 1) CRH and beta-endorphin function as a local mediator of inflammatory arthritis, 2) CRH and beta-endorphin play a role in the pathogenesis of RA.3) Antibodies against CRH and beta-endorphin may be used for therapy of RA.

  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] Crofford,L.J.: "Local expression of corticotropin releasing hormone in inflammatory arthritis." Ann.N.Y.Acad.Sci.771. 459-471 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Karalis,K.: "Somatosatin may participate in the antiinflammatory actions of glucocorticoids." Endocrinology. 136. 4133-4138 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野 統: "NOと関節炎" リウマチ科. 16. 584-595 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野 統: "COX-2の疾患における役割とCOX-2ノックアウトマウスの病態." 臨床免疫. 29. 265-273 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野 統: "炎症と免疫応答のクロストーク-プロスタノイド-" 臨床免疫. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野 統: "慢性関節リウマチにおける視床下部-下垂体-副腎軸機能異常-CRHとβ-エンドルフィンを中心に-" 臨床免疫. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hla,T.: "Role of the early response gene cyclooxygenase(COX)-2 in angiogenesis.In Angiogenesis:Molecular Biology and Clinical Aspects" Plenum Press.,N.Y.(ed by Macagondakis,M.E.)(in press),

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野 統: "慢性関節リウマチ患者滑膜におけるCOX-1およびCOX-2 mRNAの発現.リウマチ'96" メディカルレビュー社,東京(柏崎禎夫 監修), 28-38 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Crofford, L.J., Sano, H., Karalis, K., Webster, E.A., Friedman, T.C., Chrousos, G.P., Wilder, R.L.: "Local expression of corticotropin releasing hormone in inflammatory arthritis." Ann. N.Y.Acad. Sci.77. 459-471 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Karalis, K., Mastorakos, G., Sano, H., Wilder, R.L.Chrousos, G.P.: "Somatostatin may participate in the antiinflammatory actions of glucocorticoids." Endocrinology. 136. 4133-4138 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano, H., Hashiramoto, A.: "NO and Arthritis." Rheumatology. 16. 584-595 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano, H., Hashiramoto, A., Yamada, R., Fukui, W., Miyazaki, S., Mukai, S., Kimura, S., Asai, K., Kato, H., Kondo, M.Chrousos, G.P.: "Hypothalamic-pituitary-adrenal axis dysfunction in rheumatoid arthritis-beta-endorphin-." Jpn. Clin. Immunol.19. 661-663 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano, H.: "The role of Cox-2 in diseases and the pathology of COX-2 knockout mice." Clin. Immunol.29. 265-273 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano, H.: "Cross talk of inflammation and immunology-prostanoids-" Clin. Immunol.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano, H., Kawahito, Y., Hashiramoto, A., Miyazaki, S., Yamada, R., Fukui, W., Kondo, M.: "Hypothalamic-pituitary-adrenal axis dysfunction in rheumatoid arthritis-CRH and beta-endorphin-." Clin Immunol.(in press.).

    • 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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