From the Department of Endocrinology, Diabetology and Metabolism (S.A.U., F.E., M.Y.D., M.C.-C.), University Hospital Basel, Switzerland.
Department of Clinical Research (S.A.U., F.E., T.B., P.S., B.M., M.Y.D., M.C.-C.), University Hospital Basel, Switzerland.
Hypertension. 2020 Jun;75(6):1455-1463. doi: 10.1161/HYPERTENSIONAHA.119.13982. Epub 2020 Apr 10.
IL (Interleukin)-1 antagonism decreases blood pressure in obese individuals. The underlying mechanisms are unknown. Based on experimental data, we hypothesized an effect of IL-1 antagonism via modulation of the renin-angiotensin-aldosterone system. In this explorative study, we examined shorter- (2 days) and longer-term effects (4 weeks) of IL-1 antagonism (anakinra/Kineret) on renin-angiotensin system peptide profiles and on hemodynamic parameters assessed by noninvasive measurement in obese (body mass index ≥30 kg/m) individuals from 2 interventional trials (a prospective interventional trial [n=73] and a placebo controlled-double blinded interventional trial [n=67]). A total of 140 patients were included. Systolic blood pressure decreased after short-term (absolute difference -5.2 mm Hg [95% CI, -8.5 to -1.8]; =0.0006) and after longer-term treatment with anakinra (absolute difference -3.9 mm Hg [95% CI, -7.59 to -0.21]; =0.04), with no change in blood pressure in the placebo group. Upon IL-1 antagonism, equilibrium levels of Ang II (angiotensin II), Ang I, aldosterone, and renin remained unchanged. In contrast, Ang (1-7) peptide levels increased after 4 weeks (between-group difference 16.35 pmol/L [95% CI, 1.22-30.17], =0.03), as well as the Ang (1-7)/Ang II ratio (between-group difference 0.42 [95% CI, 0.17-0.67], =0.02) in comparison to placebo. Consistently, the stroke systemic vascular resistance index significantly decreased in the anakinra group (between-group difference of -62.65 dyn/sec per cm per m [95% CI, -116.94 to -18.36], =0.008, consistent with a 25% decrease). IL-1 antagonism increased the vasodilatory Ang (1-7) peptide after 4 weeks of treatment in obese individuals, paralleled by a decrease in peripheral vascular resistance. These findings point to an IL-1 mediated blood pressure-lowering mechanism via modulation of Ang (1-7). Registration- URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02227420 and NCT02672592.
白细胞介素-1 拮抗作用可降低肥胖个体的血压。其潜在机制尚不清楚。基于实验数据，我们假设白细胞介素-1 拮抗作用通过调节肾素-血管紧张素-醛固酮系统发挥作用。在这项探索性研究中，我们在两项干预试验（前瞻性干预试验[ n = 73]和安慰剂对照双盲干预试验[ n = 67]）中检查了白细胞介素-1 拮抗作用（阿那白滞素/金纳单抗）对肾素-血管紧张素-醛固酮系统肽谱和通过非侵入性测量评估的血流动力学参数的短期（2 天）和长期（4 周）影响。共有 140 名患者入选。短期（绝对差异-5.2mmHg[95%CI，-8.5 至-1.8]；=0.0006）和长期（绝对差异-3.9mmHg[95%CI，-7.59 至-0.21]；=0.04）使用阿那白滞素治疗后，收缩压降低，而安慰剂组血压无变化。在白细胞介素-1 拮抗作用下，Ang II（血管紧张素 II）、Ang I、醛固酮和肾素的平衡水平保持不变。相比之下，Ang（1-7）肽水平在 4 周后升高（组间差异 16.35pmol/L[95%CI，1.22-30.17]；=0.03），Ang（1-7）/Ang II 比值也升高（组间差异 0.42[95%CI，0.17-0.67]；=0.02）与安慰剂相比。同样，阿那白滞素组的系统性血管阻力指数明显降低（组间差异-62.65dyn/sec·cm·m[95%CI，-116.94 至-18.36]；=0.008，相当于降低 25%）。白细胞介素-1 拮抗作用在肥胖个体中增加了血管扩张性 Ang（1-7）肽，同时外周血管阻力降低。这些发现表明，白细胞介素-1 通过调节 Ang（1-7）介导了一种降低血压的机制。注册- URL：https://www.clinicaltrials.gov。独特标识符：NCT02227420 和 NCT02672592。
