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 s.c.) 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 receivedprednisolone 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<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05). CONCLUSIONS:Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.
RCT Entities:
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 s.c.) 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<0.05 for all comparisons). After 30 days of treatment, the improvement in biomarkers and in vascular and left ventricular function was greater in the anakinra group than in the prednisolone group (P<0.05). CONCLUSIONS:Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.
Authors: Fabienne Rehren; Barbara Ritter; Oliver Dittrich-Breiholz; Andreas Henke; Elena Lam; Semra Kati; Michael Kracht; Albert Heim Journal: Med Microbiol Immunol Date: 2012-06-03 Impact factor: 3.402
Authors: F Verhoeven; P Totoson; K Maguin-Gaté; A Prigent-Tessier; C Marie; D Wendling; J Moretto; C Prati; C Demougeot Journal: Clin Exp Immunol Date: 2017-03-09 Impact factor: 4.330
Authors: Antonio Abbate; Benjamin Wallace Van Tassell; Giuseppe Biondi-Zoccai; Michael Christopher Kontos; John Dallas Grizzard; Debra Whittaker Spillman; Claudia Oddi; Charlotte Susan Roberts; Ryan David Melchior; George Herman Mueller; Nayef Antar Abouzaki; Lenore Rosemary Rengel; Amit Varma; Michael Lucas Gambill; Raquel Appa Falcao; Norbert Felix Voelkel; Charles Anthony Dinarello; George Wayne Vetrovec Journal: Am J Cardiol Date: 2013-02-27 Impact factor: 2.778