Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis
Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis
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DOI：
10.1161/circulationaha.107.731877
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发表时间：
2008-05-20
期刊：
影响因子：
37.8
通讯作者：
Kremastinos, Dimitrios T.
中科院分区：
文献类型：
--
作者：
Ikonomidis, Ignatios;Lekakis, John P.;Kremastinos, Dimitrios T.
背景：白细胞介素-1增加硝基氧化应激。我们研究了重组人白细胞介素-1a受体拮抗剂（anakinra）对硝基氧化应激、血管和左心室功能的影响。方法和结果：在一项急性双盲试验中，23例类风湿关节炎患者随机接受单次注射阿那白（150 mg SC）或安慰剂，并在48小时后接受替代治疗。在基线和注射后3小时，我们使用超声心动图评估(1)冠状动脉血流储备、主动脉扩张、二尖瓣环的收缩和舒张速度（Em）和E/Em比（E/Em）；(2)血流介导的、内皮依赖性的肱动脉扩张；丙二醛、硝基酪氨酸、白细胞介素-6、内皮素-1和c反应蛋白。在一项慢性非随机试验中，23名患者接受了阿那那，19名患者接受了强的松龙治疗，持续30天，之后重新评估所有指标。与基线相比，阿那金组丙二醛、硝基酪氨酸、白细胞介素-6和内皮素-1的降低幅度更大，血流介导的舒张、冠状动脉血流储备、主动脉扩张性、二尖瓣环收缩速度和E/Em的增加幅度也比安慰剂组大(丙二醛-25%比9%；硝基酪氨酸-38%比-11%；白细胞介素-6 -29%比0.9%；内皮素-1 -36%比-11%；血流介导的舒张45%比-9%；冠状动脉血流储备29% vs 4%；主动脉扩张率45%对2%；P
Background-Interleukin-1 increases nitrooxidative stress. We investigated the effects of a human recombinant interleukin-1a receptor antagonist (anakinra) on nitrooxidative stress and vascular and left ventricular function.Methods and Results-In an acute, double-blind trial, 23 patients with rheumatoid arthritis were randomized to receive a single injection of anakinra (150 mg SC) or placebo and, after 48 hours, the alternative treatment. At baseline and 3 hours after the injection, we assessed (1) coronary flow reserve, aortic distensibility, systolic and diastolic (Em) velocity of the mitral annulus, and E to Em ratio (E/Em) using echocardiography; (2) flow-mediated, endothelium-dependent dilation of the brachial artery; and (3) malondialdehyde, nitrotyrosine, interleukin-6, endothelin-1, and C-reactive protein. In a chronic, nonrandomized trial, 23 patients received anakinra and 19 received prednisolone for 30 days, after which all indices were reassessed. Compared with baseline, there was a greater reduction in malondialdehyde, nitrotyrosine, interleukin-6, and endothelin-1 and a greater increase in flow-mediated dilation, coronary flow reserve, aortic distensibility, systolic velocity of mitral annulus, and E/Em after anakinra than after placebo (malondialdehyde -25% versus 9%; nitrotyrosine -38% versus -11%; interleukin-6 -29% versus 0.9%; endothelin-1 -36% versus -11%; flow-mediated dilation 45% versus -9%; coronary flow reserve 29% versus 4%; and aortic distensibility 45% versus 2%; P