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

我评估了环孢素在24例微小变化肾病综合征患者中的细胞药效学。计算体外环孢素浓度对刀豆蛋白A刺激的pbmc胚发生50%抑制作用（IC_<50>）。环孢素IC_<50>值与尿蛋白下降率评价临床环孢素疗效呈负相关（r=-0.708, p=0.0006）。环孢素IC_<50>与血清总胆固醇（r=0.681, p=0.0003）或低密度脂蛋白胆固醇（r=0.751, p=0.0034）浓度均显著相关。此外，血清总胆固醇或低密度脂蛋白胆固醇水平与环孢素临床疗效显著负相关（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名健康者（p<0.005），而cd3富集pbmc中ldl受体表达细胞的百分比在这些患者与健康者之间无显著差异。这些数据提高了肾病综合征患者高胆固醇血症降低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。

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.