Influence of serum lipids on lymphocyte sensitivity to immunosuppressive drugs and its clinical implication in patients with nephrosis.

肾病患者血脂对淋巴细胞对免疫抑制药物敏感性的影响及其临床意义

• 批准号: 13672402
• 负责人: HIRANO Toshihiko
• 金额: $ 1.86万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672402/
• 关键词: peripheral lymphocytes; drug sensitivity; immunosuppressive drugs; serum total cholesterol; LDL-cholesterol; cyclosporine; LDL-receptor; nephrotic syndrome; CD3陽性細胞; T細胞; 血清脂質濃度; トリグリセリド

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.

我评价了环孢素对24例微小病变型肾病综合征患者的细胞药效学。计算了对伴刀豆球蛋白A刺激的PBMC的胚细胞生成产生50%抑制的体外环孢霉素浓度（IC_<50>）。环孢素IC_<50>值与通过尿蛋白降低率评估的环孢素临床疗效呈负相关（r=-0.708，p=0.0006）。环孢素IC_<50>s与血清总胆固醇（r=0.681，p=0.0003）或LDL-胆固醇（r=0.751，p=0.0034）浓度显著相关。此外，血清总胆固醇或LDL胆固醇水平与环孢素临床疗效显著负相关（分别为r=-0.613，p=0.0057和r=-0.773，p=0.0399）。血清总胆固醇和LDL胆固醇浓度显著高于15名健康受试者（p&lt;0.005），而这些患者和健康受试者之间富含CD 3的PBMC中LDL受体表达细胞的百分比没有显著差异。这些数据提出了肾病综合征患者高胆固醇血症减弱细胞和临床环孢素药效学的可能性。PBMC对环孢素反应的个体偏差似乎与LDL受体阳性细胞数的差异无关。

项目成果

Hirano Toshihiko, Kohsaka Satoshi, Akashi Takao, Akashi Masakazu, Yoshikawa Noriko, Yoshida Masaharu, Oka Kitaro: "Influence of serum lipids on cyclosporine pharmacodynamics in patients with minimal change nephrotic syndrome."Jpn J Clin Pharmacol Ther. 35

Hirano Toshihiko、Kohsaka Satoshi、Akashi Takao、Akashi Masakazu、Yoshikawa Noriko、Yoshida Masaharu、Oka Kitaro：“微小病变肾病综合征患者血清脂质对环孢素药效学的影响。”Jpn J Clin Pharmacol Ther。