Project/Area Number |
09672337
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
応用薬理学・医療系薬学
|
Research Institution | Tokyo 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)
|
Keywords | immunosuppressants / 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.
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