| Project/Area Number |
16590125
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | Tokyo University of Pharmacy and Life Sciences |
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Principal Investigator |
HIRANO Toshihiko Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Associate Professor, 薬学部, 助教授 (90173252)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | peripheral blood lymphocytes drugs / sensitivities to immunosuppressive drugs / Staphylococcus aureus / superantigen / glucocorticoid / interleukin 2 / autoimmune diseases / organ transplantation / 腎移植 / 免疫抑制薬 / グルココルチコイド / サイトカイン / インターロイキン2mRNA / アトピー性皮膚炎 / 末梢血単核細胞 |
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| Research Abstract |
Successful immunosuppressive therapy is critical for the treatment of organ transplant recipients and patients with autoimmune diseases. However, a considerable number of patients have shown clinical resistance to therapy. Bacterial infection might influence the clinical response of patients to immunosuppressive drugs, but few studies have been carried out to investigate the effect of bacterial superantigens on the efficacy of the drugs in these patients. We evaluated the suppressive efficacy of prednisolone, methylprednisolone, cyclosporine, and tacrolimus on the blastogenesis of PBMCs obtained from patients with chronic renal; failure renal awaiting transplantation, patients with several autoimmune diseases, and healthy subjects. In vitro drug concentrations giving 50% inhibition (IC_<50s>) of PBMC blastogenesis stimulated with concanavalin A (con A) or toxic shock syndrome toxin 1 (TSST-1) derived from Staphylocuccus aureus (S. aureus) were calculated. The ICσo values for the four drugs evaluated in TSST-1-stimulated PBMCs were significantly higher than those evaluated in con A-stimulated PBMCs (p<0.05). The amount of Interleukin 2 produced from PBMCs stimulated with TSST-1was significantly larger than that produced from PBMCs stimulated with con A in both patients and healthy subjects (p<0.05). These observations raise the possibility that TSST-1 induced by S. aureus infection attenuates the clinical efficacy of glucocorticoids and calcineurin inhibitors in patients with autoimmune diseases.
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