2003 Fiscal Year Final Research Report Summary
Influence of serum lipids on lymphocyte sensitivity to immunosuppressive drugs and its clinical implication in patients with nephrosis.
| Project/Area Number |
13672402
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
HIRANO Toshihiko Tokyo University of Pharmacy and Life Science, Faculty of Pharmacy, Associate Professor, 薬学部, 助教授 (90173252)
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| Project Period (FY) |
2001 – 2003
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| Keywords | peripheral lymphocytes / drug sensitivity / immunosuppressive drugs / serum total cholesterol / LDL-cholesterol / cyclosporine / LDL-receptor / nephrotic syndrome |
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| Research Abstract |
I evaluated the cellular pharmacodynamics of cyclosporine in 24 patients with minimal change nephrotic syndrome. In vitro cyclosporine concentrations giving 50% inhibition of blastogenesis of PBMCs stimulated with concanavalin A (IC_<50>) were calculated. The cyclosporine IC_<50> values negatively correlated with the clinical cyclosporine efficacy assessed by a decreasing rate of urinary protein (r=-0.708, p=0.0006). Cyclosporine IC_<50>s significantly correlated with either serum total cholesterol (r=0.681, p=0.0003) or LDL-cholesterol (r=0.751, p=0.0034) concentrations. Furthermore, serum total-or LDL-cholesterol levels significantly correlated negatively with clinical cyclosporine efficacy (r=-0.613, p=0.0057 and r=-0.773, p=0.0399, respectively). Serum total-and LDL-cholesterol concentrations were significantly higher than those of 15 healthy subjects (p<0.005), while the percentages of LDL-receptor expressing cells in CD3-enriched PBMCs were not significantly different between these patients and healthy subjects. The data raised the possibility that hypercholesterolemia in patients with nephrotic syndrome attenuates cellular and clinical cyclosporine-pharmacodynamics. Individual deviation of PBMC-response to cyclosporine does not appear to be related to the difference of LDL-receptor positive cell numbers.
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