DePalma Ralph G, Hayes Virginia W, Cafferata H Treat, Mohammadpour Hamid A, Chow Bruce K, Zacharski Leo R, Hall Mark R
Veterans Affairs Central Office, 20420, Washington, DC 20040, USA.
J Surg Res. 2003 May 15;111(2):215-21. doi: 10.1016/s0022-4804(03)00075-1.
Iron accumulation and inflammation may affect atherosclerosis. This study intended to define a cytokine signature in atherosclerotic claudicants and to determine whether reduction in serum ferritin by phlebotomy influenced this pattern.
Ninety-one subjects with peripheral vascular disease (PVD; mean age, 67 years) were recruited from the VA Cooperative Iron and Atherosclerosis Study (FeAST) testing the hypothesis that ferritin reduction to 25 ng/ml may ameliorate atherosclerosis. Cytokines TNF-a, IL-2, IL-6, and IL-10 were analyzed by enzyme amplified sensitivity assay (EASIA). Fasting iron and cholesterol panels, complete blood count, C-reactive protein (CRP), uric acid, fibrinogen, glucose, and hemoglobin A1c levels were also quantified. Values were compared with "healthy" controls (n = 21; mean age, 56 years). After randomization of PVD to phlebotomy (intervention group [IG], n = 44) or control (nonintervention group [NG], n = 47), analyses were compared at 6 and 12 months using t test, Wilcoxon rank sum test, chi-square, and robust MM regression.
Age, glucose, and hemoglobin A1c were higher in PVD compared with healthy controls (P < 0.01), whereas serum iron (P < 0.01) and percentage of transferrin saturation (P < 0.05) were lower. Tumor necrosis factor-alpha (TNF-alpha; P < 0.05), IL-6 (P < 0.01), and CRP (P < 0.05) levels were higher in the PVD group, whereas IL-10 was lower (P < 0.01). At 6 months post phlebotomy, ferritin levels were reduced (P < 0.01), although ferritin levels were reduced less in smokers. IL-6 and fibrinogen, CRP and ferritin levels correlated positively. At 6 and 12 months, subjects with TNF-alpha (n= 15) and IL-6 (n = 10) levels in the upper 25th percentile were reduced by phlebotomy.
An inflammatory cytokine signature exists in atherosclerosis. Elevated levels of TNF-alpha and IL-6, reportedly associated with recurrent and future myocardial infarction, were reduced by phlebotomy. The utility of the iron/inflammatory hypotheses will ultimately relate to clinical outcomes obtained prospectively by the FeAST trial.
铁蓄积和炎症可能影响动脉粥样硬化。本研究旨在确定动脉粥样硬化性间歇性跛行患者的细胞因子特征，并确定通过放血降低血清铁蛋白是否会影响这种模式。
从退伍军人事务部合作铁与动脉粥样硬化研究（FeAST）中招募了91名外周血管疾病（PVD；平均年龄67岁）患者，该研究检验了铁蛋白降低至25 ng/ml可能改善动脉粥样硬化的假设。通过酶放大敏感性分析（EASIA）分析细胞因子TNF-α、IL-2、IL-6和IL-10。还对空腹铁和胆固醇指标、全血细胞计数、C反应蛋白（CRP）、尿酸、纤维蛋白原、葡萄糖和糖化血红蛋白水平进行了定量。将这些值与“健康”对照组（n = 21；平均年龄56岁）进行比较。将PVD患者随机分为放血组（干预组[IG]，n = 44）或对照组（非干预组[NG]，n = 47），在6个月和12个月时使用t检验、Wilcoxon秩和检验、卡方检验和稳健MM回归进行分析比较。
与健康对照组相比，PVD患者的年龄、葡萄糖和糖化血红蛋白更高（P < 0.01），而血清铁（P < 0.01）和转铁蛋白饱和度百分比（P < 0.05）更低。PVD组肿瘤坏死因子-α（TNF-α；P < 0.05）、IL-6（P < 0.０1）和CRP（P < 0.05）水平更高，而IL-10更低（P < 0.01）。放血后6个月，铁蛋白水平降低（P < 0.01），尽管吸烟者的铁蛋白水平降低较少。IL-6与纤维蛋白原、CRP与铁蛋白水平呈正相关。在6个月和12个月时，放血使TNF-α（n = 15）和IL-6（n = 10）水平处于上四分位数的患者减少。
动脉粥样硬化中存在炎症细胞因子特征。据报道，与复发性和未来心肌梗死相关的TNF-α和IL-6水平通过放血降低。铁/炎症假说的效用最终将与FeAST试验前瞻性获得的临床结果相关。
