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1999 Fiscal Year Final Research Report Summary

Study for molecular and gene therapy of rheumatoid arthritis by targeting IL-6 signal transduction.

Research Project

Project/Area Number 10470126
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionOsaka University

Principal Investigator

NISHIMOTO Norihiro  School of Health and Sport Sciences, Osaka University Associate Professor, 健康体育部, 助教授 (80273663)

Co-Investigator(Kenkyū-buntansha) OCHI Takahiro  Graduate School of Medicine, Osaka University, Professor, 医学系研究科, 教授 (80112035)
YOSHIZAKI Kazuyuki  School of Health and Sport Sciences, Osaka University, Professor, 健康体育部, 教授 (90144485)
MATSUMOTO Tomoshige  School of Health and Sport Sciences, Osaka University, Assistant Professor, 健康体育部, 助手 (10311763)
Project Period (FY) 1998 – 1999
KeywordsRheumatoid Arthritis / Cytokine / Interleukin 6 (IL-6) / TNFα / Humanized Antibody / IL-6 receptor / SSI-1 / Negative feedback
Research Abstract

1. Inhibitory effects of anti-interleukin-6 receptor antibody (anti-IL-6R Ab) against murine and similar collagen-induced arthritis and joint destruction were elucidated.
2. Humanized anti-IL-6R Ab was proven to be effective to patients with refractory rheumatoid arthritis (RA) and thus confirming that IL-6 plays a major role in the RA pathology. It also shows IL-6 signal blocking can be a new therapy for RA.
3. IL-6 in the presence of soluble IL-6R (sIL-6R) inhibits the growth of synovial cells. TNFα-induced IL-6 can be a negative feedback factor of TNFα-induced synovial cell proliferation in RA.
4. Therapeutic effects of IL-6 blockade were through elimination of inflammatory cell penetrating the RA synovial tissue and also through inhibition of angiogenesis and osteoclast formation.
5. STATs-induced STATs inhibitor-1 and its family molecule SSI-3 as negative feed back factors of intracytoplasmic IL-6 signaling may be involved in the chronic inflammatory status of RA.
6. These results indicate the possibility of new therapeutic approach for RA by blocking IL-6 signaling based on the pathophysiology of RA.

  • Research Products

    (67 results)

All Other

All Publications (67 results)

  • [Publications] Takagi N., N. Mihara, Y. Moriya, N. Nishimoto, K. Yoshizaki, T. Kishimoto, Y. Takeda, Ohsugi Y.: "Blockage of Interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis"Arthritis Rheum. 41. 2117-2121 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsuno H., Sawai T., Uzuki M., Tsuji H., Nishimoto N., Yoshizaki K: "Treatment of rheumatoid synovitis with anti-reshaping human Interleukin-6 receptor monoclonal antibody-use of Rheumatoid Arthritis tissues implants in the SCID mouse model"Arthritis Rheum. 41. 2014-2021 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Isumi Y., N. Minamoto, A. Kubo, N. Nishimoto, K. Yoshizaki, M. Yoshika, K. Kangawa, H. Matsuo: "Adrenomedullin stimulates IL-6 production in Swiss 3T3 cells"Biochem. Biophys. Res. Co.. 244. 325-331 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Johkoh T, N. L. Miller, K. Ichikado, N. Nishimoto, K. Yoshizaki, et al.: "Intrathoracic multicentric castleman disease : CT findings in 12 patient"Radiology. 209. 477-481 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoshizaki K., Nishimoto N., Mihara M., Kishimoto T: "Therapy of RA by blocking IL-6 signal transduction with humanized anti-IL-6 receptor antibody"Springer Seminars in immunopathology. 20. 247-259 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸,岸本忠三: "サイトカインシグナル伝達阻害による自己免疫疾患の治療"日本内科学会雑誌. 87. 1745-1750 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsue H., T. Sakakibara, R. Matsuwaka, M. Mitsuno, M. Tsujimoto, N. Nishimoto: "Malignant fibrous histiocytoma of the heart producing Interleukin-6"Journal of Thoracic & Cardiovascular Surgery. 116. 522-524 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤愛,田合ひろみ,西本憲弘,吉崎和幸: "RAの先進医療〜IL-6レセプターを阻害する治療法〜"RA&セラピー. 4. 42-51 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "抗サイトカイン療法とその有用性"Medical Practice. 15. 2105-2108 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "慢性関節リウマチの抗IL-6レセプター抗体療法"リウマチ科. 19. 399-402 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸,岸本忠三: "抗IL-6抗体による骨髄腫瘍細胞の増殖制御"臨床検査. 42. 86-89 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "サイトカインとサイトカインレセプター"臨床免疫. 30. 1370-1375 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉崎和幸,西本憲弘: "ヒト型化抗IL-6レセプター抗体によるキャッスルマン氏病の治療"感染・炎症・免疫. 28. 42-43 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉崎和幸,西本憲弘,田合ひろみ,松本智成: "ヒト型化抗IL-6レセプター抗体を用いたIL-6シグナル伝達阻害によるキャッスルマン病の治療への応用"炎症. 18. 319-326 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤 愛,西本憲弘,團野典行,大野美夏,吉崎和幸: "インターロイキン6の病態における役割と治療への応用"Cardiologist. 3. 113-119 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimoto N., Yoshizaki K., and Kishimoto T.: "Anticytokine therapy in autoimmune diseases"Internal Medicine. 38. 178-182 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimoto, N., Sasai, M., Shima, Y., Nakagawa, M., Matsumoto, T., Shirai, T., Kishimoto, T., and Yoshixzaki, K.: "Improvement in Castleman's by humanized anti-Interleukin-6 receptor antibody therapy"Blood. 95. 56-61 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishimoto, N., A. Ito., M. Ono., H. Tagoh., T. Matsumoto., T. Tomita., T, Ochi, and Y. Yoshizaki: "IL6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor"International Immunology. 12. 187-193 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mori, Y., Nishimoto, N., Ohno, K., Inagi, P., Dhepakson, K., Amou, K., Yoshizaki and K. Yamanishi: "Human Herpevirus 8-encoded Interleukin-6 homologue (viral IL-6) induces endogeneous human IL-6 secretion"J. Med. Virol.. (in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "慢性関節リウマチ抗サイトカイン療法をめぐって"現代医療. 31. 192-196 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "IL-6阻害による多発性骨髄腫治療"細胞. 31. 362-365 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉崎和幸,松本智成,橋本 淳,松野博明,冨田哲也,超智隆弘,西本憲弘: "ヒト型化抗インターロイキン6抗体によるインターロイキン6のシグナル阻害による骨粗鬆症の発症予防と治療法の開発"協栄生命研究助成論文集. 15. 45-49 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "ヒトヘルペスウイルス8感染とBリンパ球増殖性疾患"最新医学9月増刊号 臨床遺伝子学'99. 54. 283-287 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "抗サイトカイン療法-現状と将来の展望-"Pharma Medica. 17. 95-100 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,松本智成,吉崎和幸: "抗サイトカイン療法"カレントテラピー. 17. 150-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,松本智成,橋本 淳,松野博明,冨田哲也,超智隆弘,吉崎和幸: "インターロイキン6のシグナル伝達阻害による骨粗鬆症の治療法の開発"Osteoporosis Japan. 7. 34-37 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "Castleman病とMCD -IL-6シグナル阻害による治療-"医学のあゆみ. 188. 942-948 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 松本智成,西本憲弘,吉崎和幸: "慢性関節リウマチにおける抗IL-6レセプター療法"炎症と免疫. 8. 100-103 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 中原英子,西本憲弘,松本智成,吉崎和幸: "感染とIL-6"臨床と微生物. (in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "リウマチ病セミナーX.TNFαおよびIL-6阻害による慢性関節リウマチの新しい治療法"永井書店. 361 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "新臨床医のための分子医学シリーズ・サイトカインと疾患.ウイルス感染とサイトカイン(in press)"医科学図書出版. (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 吉崎和幸,西本憲弘: "Moleculra Medicin臨時増刊号症候・病態のメカニズム.骨融解像."中山書店. 606 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 西本憲弘,吉崎和幸: "生物学的製剤.免疫抑制剤の使い方"南江堂(in press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takagi, N., M. Mihara, Y. Moriya, N. Nishimoto, K. Yoshizaki, T. Kishimoto, Y. Takeda, and Y. Ohsugi.: "Blockage of Interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis"Arthritis Rheum. 41. 2117-2121 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Isumi, Y., N. Minamino, A. Kubo, N. Nishimoto, K. Yoshizaki, M. Yoshioka, K. Kangawa, and H. Matuso.: "Adrenomedullin stimulates IL-6 production in Swiss 3T3 cells."Biochem. Bioph. Res. Co.. 244. 325-331 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsuno, H., T. Sawai, T. Nezuka, M. Uzuki, H. Tsuji, N. Nishimoto, and K. Yoshizaki.: "Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody-use of Rheumatoid Arthritis tissues implants in the SCID mouse model."Arthritis Rheum. 41. 2014-2021 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsue, H., T. Sakakibara, R. Matsuwaka, M. Mitsuno, M. Tsujimoto, and N. Nishimoto.: "Malignant fibrous histiocytoma of the heart producing interleukin-6."Journal of Thoracic & Cardiovascular Surgery. 116. 522-524 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Johkoh, T., N. L. Muller, K. Ichikado, N. Nishimoto, K. Yoshizaki, O. Honda, N. Tomiyama, H. Naitoh, H. Nakamura, and S. Yamamoto.: "Intrathoracic multicentric castleman disease : CT findings in 12 patient."Radiology. 209. 477-481 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Johkoh, T., N. L. Muller, K. Ichikado, N. Nishimoto, K. Yoshizaki, O. Honda, N. Tomiyama, H. Naitoh, H. Nakamura, and S. Yamamoto.: "Intrathoracic multicentric castleman disease : CT findings in 12 patient."Internal. Med. 38. 178-182 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto, N., K. Yoshizaki, and T. Kishimoto.: "Anticytokine therapy in autoimmune diseases."Internal. Med.. 38. 178-182 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizaki, K., N. Nishimoto, M. Mihara, and T. Kishimoto.: "Therapy of RA by blocking IL-6 signal transduction with humanized anti-IL-6 receptor antibody."Springer Seminars in immunopathology. 20. 247-259 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto, N., M. Sasai, Y. Shima, M. Nakagawa, T. Matsumoto, T. Shirai, T. Kishimoto, and K. Yoshizaki.: "Improvement in Castleman's by humanized anti-Interleukin-6 receptor antibody therapy."Blood. 95. 56-61 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto, N., A. Ito, M. Ono, H. Tagoh, T. Matsumoto, T. Tomita, T. Ochi, and K. Yoshizaki.: "IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor."Int. Immunol.. 12. 187-193 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mori, Y., N. Nishimoto, M. Ono, R. Inagi, P. Dhepakson, K. Amou, K. Yoshizaki, and K. Yamanishi.: "Human Herpesvirus 8-encoded Interleukin-6 homologue (viral IL-6) induced endogeneous human IL-6 secretion."J. Med. Virol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., K. Yoshizaki, and T. Kishimoto.: "Therapy for autoimmune disease by blocking cytokine signaling."Nihon Naikagakkai Zasshi. 87. 1745-1750 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito A, N. Nishimoto, H. Tagoh, and K. Yoshizaki.: "Advanced therapy for RA-IL-6 receptor blockade-."RA & Therapy. 4. 42-51 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Anti-IL-6 receptor therapy for rheumatoid arthritis."Riumachi-ka. 19. 399-402 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., K. Yoshizaki, and T. Kishimoto.: "Inhibition of myeloma cell growth by anti-IL-6R antibody."Rinsho-kensa. 42. 86-89 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Cytokine and cytokine receptor."Rinsho-meneki. 30. 1370-1375 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizaki K., and N. Nishimoto.: "Therapy for Castleman's disease by humanized anti-IL-6 receptor antibody."Kansen Ensho Meneki. 28. 42-43 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizaki K., N. Nishimoto, H. Tagoh, T. Matsumoto.: "Therapeutic approach for Castleman's disease by blocking IL-6 signal utilizing humanized anti-IL-6 receptor antibody."Ensho. 18. 319-326 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito A, N. Nishimoto. Danno, M. Ohno, and K. Yoshizaki.: "Pathological roles of interleukin 6 and therapeutic application."Cardiologist. 3. 113-119 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Rheumatoid arthritis-anti-cytokine therapy-."Gendai-iryo. 31. 192-196 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "IL-6-blocking therapy for multiple myeloma."Saibo. 31. 362-365 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshizaki K., T. Matsumoto, J. Hashimoto, H. Matsuno, T. Tomita, T. Ochi, and N. Nishimoto.: "Prevention and therapy for osteoporosis by blocking interleukin-6 signal utilizing humanized anti-interleukin 6 antibody."Kyoei-seimei Kenkyu-josei Ronbunshu. 15. 45-49 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Human Herpes-virus 8 infection and B lymphocyte proliferative disease."Rinsho-iden-gaku'99, Saishinigaku. 54. 283-287 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Anti-cytokine therapy-present and future status--."Pharma Medica. 17. 95-100 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., T. Matsumoto, J. Hashimoto, H. Matsuno, T. Tomita, T. Ochi, and K. Yoshizaki.: "Development of osteoporosis therapy by blocking interleukin 6 signal."Osteoporosis Japan. 7. 34-37 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Castleman's disease and MCD--IL-6 signal-blocking therapy-"Igaku no Ayumi. 188. 942-948 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsumoto T., N. Nishimoto and K. Yoshizaki: "Anti-IL-6 receptor therapy in rheumatoid arthritis."Ensho to Meneki. 8. 100-103 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakahara H, N. Nishimoto, T. Matsumoto, and K. Yoshizaki: "Infection and IL-6."Rinsho to Biseibutsu. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Anti-IL-6 receptor therapy for rheumatoid arthritis."Riumachi-ka. 19. 399-402 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., T. Matsumoto, and K. Yoshizaki.: "Anti-cytokine therapy"Current therapy. 17. 150-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Mechanisms of symptoms and pathology Osteolytic phenomenum."Molecular Medicine, Nakayama Shoten. 606 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Seminars in Rheumatic Disease X. New therapy for rheumatoid arthritis by blockade of TNFα and IL-6."Seminars in Rheumatic Disease X, Nagaishoten. 361 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "Viral infection and cytokine in cytokine and diseases."New Series molecular medicine for clinician, Yodosha. 146 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishimoto N., and K. Yoshizaki.: "How to use immunosupressant : Biological products."Nankodo (in press)..

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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