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2004 Fiscal Year Final Research Report Summary

Analysis on Mechanism of Immunomodulatory Activity Through Apoptosis Induced by Statins

Research Project

Project/Area Number 15591062
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionJichi Medical School

Principal Investigator

OKAZAKI Hitoaki  Jichi Medical School, Medicine, Associate Professor, 医学部, 助教授 (40285789)

Co-Investigator(Kenkyū-buntansha) NAGASHIMA Takao  Jichi Medical School, Medicine, Instructor, 助手 (90382861)
Project Period (FY) 2003 – 2004
Keywordsstatins / Fluvastatin / MRL-lpr / lpr mice / SLE / apoptosis
Research Abstract

Objective : Hydroxy-Methylglutaryl Coenzyme A(HMG-CoA) reductase inhibitors (statins) possesses anti-inflammatory and immunomodulatory effects. Its efficacy was demonstrated by in vivo model of collagen induced arthritis(CIA), and experimental allergic encephalitis(EAE) model mouse. To elucidate beneficial effects of statins on another autoimmune diseases, we conducted an in vivo treatment of MRL-lpr/lpr mouse, Fas deficient human Systemic lupus Erythematosus(SLE) model mouse by Fluvastatin.
Methods : female MRL-lpr/lpr mice age between 4-5weeks were devided into 3 groups(n=20/group) : On 16 weeks, each group was administered intraperitonially with saline(control, C), Fluvastatin 10mg/kg(F), or methylprednisolone 10mg/kg(P) 3 times a week. Effects were evaluated by urine proteins, urine occult blood, anti-double strand antibody, serum creatinine, creatine phosphokinase, total cholesterol level, IFN-gamma, and survival rate.
Result s: Eight weeks after treetment, Urinary proteins(C=1.17,F=0.47), urine occult blood(C=1.44,F=0.58), serum cholesterol level(C=234.8,F=179.8), and interferon gamma (C=41.3ng/ml, F=18.7ng/ml). were decreased in Fluvastatin treated group than in control group. Elevation of creatine phosphokinase was not observed. Four months after treatment, although it was not statistically significant, there was a tendency that Fluvastatin treated group showed a better survival rate than control group.
Conclusion : There is a possibility that fluvastatin shifts Th1/Th2 balance towards Th2 by decreasing IFN-gamma, thereby improves their urinary findings, and even their survival rate.

  • Research Products

    (12 results)

All 2005 2004 2003

All Journal Article (12 results)

  • [Journal Article] Rapidly aggravated Mycobacterium avium infection in a patient with rheumatoid arthritis treated with infliximab.2005

    • Author(s)
      Okubo H, Iwamoto M, Yoshio T, Okazaki H, et al.
    • Journal Title

      Mod.Rheumatol. 15

      Pages: 62-64

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Kikuchi's disease involving the supraclavicular lymph nodes and associated with transient eruption.2005

    • Author(s)
      Kamimura T, Hatakeyama M, Okazaki H, Minota S.
    • Journal Title

      Rheumatol.Int. 25

      Pages: 143-145

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rapidly aggravated Mycobacterium avium infection in a patient with rheumatoid arthritis treated with infliximab.2005

    • Author(s)
      Okubo H, Iwamoto M, Yoshio T, Okazaki H, Kato T, Bandoh M, Minota S.
    • Journal Title

      Mod.Rheumatol. 15

      Pages: 62-64

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nocardia arthritidis sp. nov., a new pathogen isolated from a patient with rheumatoid arthritis in Japan.2004

    • Author(s)
      Kageyama A, Torikoe K, Iwamoto M, Masuyama J-I, Shibuya Y, Okazaki H, et al.
    • Journal Title

      J.Clin.Microbiol. 42

      Pages: 2366-2371

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Acute gout attack in the wrist joint2004

    • Author(s)
      Kamimura T, Hatakeyama M, Okazaki H, et al.
    • Journal Title

      Inter.Med. 43

      Pages: 641-642

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Rheumatoid arthritis complicated with acute interstitial pneumonia induced by Leflunomide as an adverse reaction.2004

    • Author(s)
      Kamata Y, Nara H, Kamimura T, Haneda K, Iwamoto M, Masuyama J, Okazaki H, et al.
    • Journal Title

      Inter.Med. 43

      Pages: 1201-1204

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] スタチン類の免疫抑制作用2004

    • Author(s)
      岡崎仁昭, 長嶋孝夫, 蓑田清次
    • Journal Title

      日本臨床免疫学会誌 27

      Pages: 357-360

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nocardia arthritidis sp.nov., a new pathogen isolated from a patient with rheumatoid arthritis in Japan.2004

    • Author(s)
      Kageyama A, Torikoe K, Iwamoto M, Masuyama J-I, Shibuya Y, Okazaki H, Yazawa K, Minota S, Kroppenstedt RM, Mikami Y.
    • Journal Title

      J.Clin.Micrbiol. 42

      Pages: 2366-2371

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Acute gout attack in the wrist joint.2004

    • Author(s)
      Kamimura T, Hatakeyama M, Okazaki H, Minota S.
    • Journal Title

      Inter.Med. 43

      Pages: 641-642

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rheumatoid arthritis complicated with acute interstitial pneumonia induced by leflunomide as an adverse reaction.2004

    • Author(s)
      Kamata Y, Nara H, Kamimura T, Haneda K, Iwamoto M, Masuyama J, Okazaki H, Minota S.
    • Journal Title

      Inter.Med. 43

      Pages: 1201-1204

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Serum levels of vasoactive intestinal peptide are elevated in patients with atopic dermatitis2003

    • Author(s)
      Umemoto N, Kakurai M, Okazaki H, et al.
    • Journal Title

      J.Dermatological.Science. 31

      Pages: 161-164

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Serum levels of vasoactive intestinal peptide are elevated in patients with atopic dermatitis.2003

    • Author(s)
      Umemoto N, Kakurai M, Okazaki H, Kiyosawa T, Demitsu T, Nakagawa H.
    • Journal Title

      J.Dermatological.Science. 31

      Pages: 161-164

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

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Published: 2006-07-11  

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