辛伐他汀和氟伐他汀可降低慢性肾病患者分离出的人单核细胞经脂多糖（LPS）刺激产生的白细胞介素-6和白细胞介素-8。
Simvastatin and fluvastatin reduce interleukin-6 and interleukin-8 lipopolysaccharide (LPS) stimulated production by isolated human monocytes from chronic kidney disease patients.
作者信息
Mantuano Emanuela, Santi Samuele, Filippi Cristina, Manca-Rizza Giovanni, Paoletti Sabrina, Consani Cristina, Giovannini Luca, Tramonti Gianfranco, Carpi Angelo, Panichi Vincenzo
机构信息
Department of Internal Medicine, Nephrology Section, University of Pisa, Italy.
出版信息
Biomed Pharmacother. 2007 Jul;61(6):360-5. doi: 10.1016/j.biopha.2007.03.002. Epub 2007 Apr 3.
BACKGROUND
Statins reduce lipid levels, inflammation and cardiovascular events in patients with coronary artery disease; CKD patients show increased risk of cardiovascular and increased plasma levels of IL-6 and IL-8.
AIM
To evaluate the in vitro effect of simvastatin (S) or fluvastatin (F) on the lipopolysaccharide (LPS) stimulated secretion of IL-6 and IL-8 from monocytes of chronic kidney disease patients (CKD) in K-DOQI stages 3-5.
METHODS AND SUBJECTS
Monocytes enriched peripheral blood (PBMC) from 28 CKD (15 in K-DOQI stages 3-4, Group I, and 13 in K-DOQI stage 5 on hemodialysis, Group II) and 10 healthy subjects (HS), were isolated by Ficoll-gradient centrifugation. Cells were incubated with LPS 100 ng/ml or with LPS plus increasing doses of statins (from 10(-6) to 10(-8) M ) for 24 h. Surnatant IL-6 and IL-8 concentrations were determined by EIA.
RESULTS
Basally the mean concentration of IL-6 and IL-8 was higher in patients than in HS and in Group II than in Group I (IL6: HS 285 +/- 77 pg/ml, Group I 365 +/- 178 pg/ml, Group II 520 +/- 139 pg/ml- IL8 HS 180 +/- 75 pg/ml, Group I 1722 +/- 582 pg/ml, Group II 4400 +/- 1935 pg/ml). After addition of LPS the mean concentration of IL-6 and IL-8 increased in all groups (IL6: HS 1740 +/- 178 pg/ml, Group I 3754 +/- 672 pg/ml, Group II 4800 +/- 967 pg/ml; IL8: HS 450+/-132 pg/ml, Group I 9700+/-2837 pg/ml, Group II 11608 +/- 2316 pg/ml). After the addition of LPS plus increasing doses of S or F from 10(-10) to 10(-6) M, a significantly lower cytokine concentration compared to the data after LPS alone was observed (IL6: HS 45%, Group I 75%, Group II 50%; IL8: HS 100%, Group I 65%, Group II 35%).
CONCLUSIONS
These data confirm that cytokine release is increased in CKD patients and that is highest in the most severe patients. Furthermore they suggest that fluvastatin or simvastatin can be used in order to reduce the high cardiovascular risk.
背景
他汀类药物可降低冠心病患者的血脂水平、炎症反应及心血管事件发生率；慢性肾脏病（CKD）患者心血管疾病风险增加，且白细胞介素 - 6（IL - 6）和白细胞介素 - 8（IL - 8）血浆水平升高。
目的
评估辛伐他汀（S）或氟伐他汀（F）对脂多糖（LPS）刺激的K - DOQI 3 - 5期慢性肾脏病患者（CKD）单核细胞分泌IL - 6和IL - 8的体外作用。
方法与研究对象
通过Ficoll梯度离心法从28例CKD患者（15例处于K - DOQI 3 - 4期，为I组；13例处于K - DOQI 5期且接受血液透析，为II组）和10例健康受试者（HS）中分离出富含单核细胞的外周血单个核细胞（PBMC）。将细胞与100 ng/ml LPS或LPS加递增剂量的他汀类药物（从10⁻⁶至10⁻⁸ M）孵育24小时。通过酶联免疫吸附测定法（EIA）测定上清液中IL - 6和IL - 8的浓度。
结果
基础状态下，患者体内IL - 6和IL - 8的平均浓度高于健康受试者，且II组高于I组（IL - 6：HS为285 ± 77 pg/ml，I组为365 ± 178 pg/ml，II组为520 ± 139 pg/ml；IL - 8：HS为180 ± 75 pg/ml，I组为1722 ± 582 pg/ml，II组为4400 ± 1935 pg/ml）。添加LPS后，所有组中IL - 6和IL - 8的平均浓度均升高（IL - 6：HS为1740 ± 178 pg/ml，I组为3754 ± 672 pg/ml，II组为4800 ± 967 pg/ml；IL - 8：HS为450 ± 132 pg/ml，I组为9700 ± 2837 pg/ml，II组为11608 ± 2316 pg/ml）。添加LPS加从10⁻¹⁰至10⁻⁶ M递增剂量的S或F后，与仅添加LPS后的数据相比，细胞因子浓度显著降低（IL - 6：HS降低45%，I组降低75%，II组降低50%；IL - 8：HS降低100%，I组降低65%，II组降低35%）。
结论
这些数据证实CKD患者细胞因子释放增加，且在病情最严重的患者中最高。此外，这些数据提示氟伐他汀或辛伐他汀可用于降低高心血管疾病风险。
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