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Study on individual immunosuppressive therapy based on peripheral-blood lymphocyte-sensitivity to immunosuppressive drugs and the mechanisms on drug resistance

Research Project

Project/Area Number 09672337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTokyo University of Pharmacy and Life Science

Principal Investigator

HIRANO Toshihiko  Tokyo University of Pharmacy & Life Science, Department of clinical Pharmacology, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (90173252)

Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Keywordsimmunosuppressants / peripheral lymphocytes / drug sensitivity / antoimmune disorders / renal transplantation / individualized drug therapy / resistant mechanisms / nephrotic syndrome / 気管支喘息 / 潰瘍性大腸炎 / グルココルチコイド受容体 / 血清コレステロール / 薬剤耐性 / サイトカイン / アポトーシス / 末梢血リンパ球 / 薬剤感受性 / 免疫抑制剤 / マイトゲン試験法
Research Abstract

This study was carried out to establish pharmacodynamic indices for effective and safety use of immunosuppressive drugs in various immunological disorders. To evaluate individual response to immunosuppressive drugs, we examined lymphocyte suppressive potency of glucocorticoids (prednisolone and methylprednisolone) and immunosuppressants (cyclosporine and tacrolimus) in vitro by use of peripheral-blood lymphocytes obtained from patients with autoimmune disorders including bronchial asthma, rheumatoid arthritis, nephrosis, ulcerative colitis, and renal transplant recipients. We also examined molecular basis for lymphocyte-resistance to immunosuppressive drugs. Lymphocyte sensitivity to immunosuppressants in vitro correlated with clinical efficacy of the drugs in patients of each disease. There may be some different mechanisms for lymphocyte-resistance between these diseases. We concluded that clinical efficacy of immunosuppressants can be predicted by measuring in vitro response of patient's lymphocytes to the drugs. The patients with lymphocytes exhibiting high-sensitivity to the drug might be treated with shorter periods or amounts of the drug, whereas the patients showing lymphocyte resistance to the drug might be refractory to the therapy. The data of in vitro sensitivity to the drugs could be an index for selection of appropriate immunosuppressant to individual patient.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Toshihiko Hirano: "Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis and psoriasis."Clinical Pharmacology and Therapeutics. 62. 652-664 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hironori Takeuchi: "Lymphocyte-sensitivities to cyclosporine and tacrolimus in chronic renal failure patients and their significance on renal transplantation."Transplantation Proceedings. 30. 36-39 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "Individual Pharmacodynamics assessed by antilymphocyte action predicts clinical cyclosporine-efficacy in psoriasis."Clinical Pharmacology and Therapeutics. 63. 465-470 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Horigome: "Tacrolimus-induced apoptosis and its prevention by inter leukins in mitogen-activated human peripheral mononuclear cells."Immunopharmacology. 39. 21-30 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma."Immunopharmacology. 40. 57-66 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Atsushi Horigome: "Lymphocyte-sensitivity to glucocorticoid correlates with the sensitivity to cyclosporine A and tacrolimas in chronic renal failure"British Journal of Clinical Pharmacology. 48. 573-578 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "A comparison of prednisolone and methylprednisolone for renal transplantation."Clinical Transplantation. 14. 323-328 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "Comparative study of lymphocyte suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis."Immunopharmacology. 49. 411-417 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "Clinical impact of cyclosporine cellular-pharmacodynamics in minimal change nephrotic syndrome."Clinical Pharmacology and Therapeutics. 68. 532-540 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Toshihiko Hirano: "Serum cholesterol levels and kidney transplantation outcome : attenuation of cyclosporine efficacy."Transplantation. 71(in press). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Oka K, Takeuchi H, Kozaki K, Matsuno N, Nagao T, Kozaki M, Ichikawa M, Yoshida M, Umezawa Y, Hirata M, Oh-i T, and Koga M.: "Immunosuppressant pharmacodynamics on lymphocytes from healthy subjects and patients with chronic renal failure, nephrosis and psoriasis : possible implications for individual therapeutic efficacy."Clin Pharmacol Ther. 62. 652-664 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takeuchi H, Hirano T, Oka K, Mizumoto K, Akashi T, Uchiyama M, Degawa T, Kozaki K, Matsuno N, Nagao T, Kozaki M, and Sakurai E.: "Lymphocyte-sensitivities to cyclosporine and tacrolimus in chronic renal failure patients and their significance on renal transplantation."Transplant Proc. 30. 36-39 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Oka K, Umezawa Y, Hirata M, Oh-i T, and Koga M.: "Individual pharmacodynamics assessed by antilymphocyte action predicts clinical cyclosporine-efficacy in psoriasis."Clin Pharmacol Ther. 63. 465-470 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horigome A, Hirano T, and Oka K.: "Tacrolimus-induced apoptosis and its prevention by interleukins in mitogen-activated human peripheral mononuclear cells."Immunopharmacology. 39. 21-30 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Homma M, Oka K, Tsushima H, Niitsuma T, and Hayashi T.: "Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma : Comparison of potencies for five glucocorticoids."Immunopharmacology. 40. 57-66 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Horigome A, Hirano T, Oka K, Takeuchi H, Kozaki K, Matsuno N, Nagao T and Kozaki M.: "Lymphocyte-sensitivity to glucocorticoid correlates with the sensitivity to cyclosporine A and tacrolimus in chronic renal failure patients."Br J Clin Pharmacol. 48. 573-578 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Oka K, Takeuchi H, Sakurai E, Kozaki K, Matsuno N, Kozaki M, Nagao T.: "A comparison of prednisolone and methylprednisolone for renal transplantation."Clin Transplantation. 14. 323-328 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Tsuboi N, Homma M, Oka K, Takekoshi T, Tahara K, Takanashi H, Abe H, Urata T, Hayashi T.: "Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis."Immunopharmacology. 49. 411-417 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Akashi T, Keira T, Oka K, Ihoya N, Yoshida M.: "Clinical impact of cyclosporine cellular-pharmacodynamics in minimal change nephrotic syndrome."Clin Pharmacol Ther. 68. 532-540 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T, Akashi T, Oka K, Yoshida M, Matsuno N, Nagao T.: "Serum cholesterol levels and kidney transplantation outcome : Attenuation of cyclosporine efficacy?"Transplantation. 71 (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirano T: "Comparative study of lymphocyte-suppressive potency between prednisolone and methylprednisolone in rheumatoid arthritis."Immunopharmacology. 49. 411-417 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirano T: "A comparison of prednisolone and methylprednisolone for renal transplantation."Clinical Transplantation. 14. 323-328 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirano T: "Clinical impact of cyclosporine cellular pharmacodynamics in minimal change nephrotic syndrome."Clinical Pharmacology and Therapeutics. 68. 532-540 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Horigome A.: "Lymphocyte-sensitivity to glucocerticoid correlates with the sensitivity to cyclosporin A and tacrolimus in chronic renal failure patients"Br J Clin Pharmacol. 48. 573-578 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hirano T.: "Individual pharmacodynamics assessed by antilymphocyte action predicts clinical cyclosporine efficacy in psoriasis." Clin Pharmacol Ther. 63・4. 465-470 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Horigome A.: "Tacrolimus-induced apoptosis and its prerention by interleulsins in mitogen-activated mononuclear cells." Immunopharmacology. 39. 21-30 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirano T.: "Individual variations in lymphocyte-responses toglucocorticoids in patients with bronchial asthma." Immunopharmacology. 40. 57-66 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeuchi H: "Lymphocyte sensitivities to cyclosporine and tacrolimus in chronic renal failure patients and their clinical significance on renal transplantation" Transplantation Proceedings. 30. 36-39 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirano T: "Immunosuppressant pharmacodynamics on lymphocyte from healthy subjects and patients with chronic renal failure,nephrosis,and psoriasis" Clinical Pharmacology and Therapeutics. 62 (6). 652-664 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hirano T: "Clinical Relevance of Glucocorticoid Pharmacodynamics in Kidney Transplantation" Transplantation. 64 (5). 792-793 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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