Inhibition of Interleukin-1 by Anakinra Improves Vascular and Left Ventricular Function in Patients With Rheumatoid Arthritis

• Published in: Circulation (New York, N.Y.) Vol. 117; no. 20; pp. 2662 - 2669
• Main Authors: IKONOMIDIS, Ignatios, LEKAKIS, John P, NIKOLAOU, Maria, PARASKEVAIDIS, Ioannis, ANDREADOU, Ioanna, KAPLANOGLOU, Theophania, KATSIMBRI, Pelagia, SKARANTAVOS, Grigorios, SOUCACOS, Panayiotis N, KREMASTINOS, Dimitrios T
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 20.05.2008
• Subjects: Adult; Aged; Arthritis, Rheumatoid - drug therapy; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Vessels - drug effects; Cardiology. Vascular system; Cross-Over Studies; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Endothelins; Female; Humans; Interleukin 1 Receptor Antagonist Protein - administration & dosage; Interleukin 1 Receptor Antagonist Protein - pharmacology; Interleukin-1 - antagonists & inhibitors; Male; Medical sciences; Middle Aged; Nitric Oxide; Oxidative Stress - drug effects; Recombinant Proteins; Ventricular Function, Left - drug effects; Human; Immunopathology; inhibitors; Cytokine; Diseases of the osteoarticular system; Autoimmune disease; Cardiovascular disease; Inflammatory joint disease; Inflammation; Endothelium; interleukins; Immunomodulator; Microcirculation; Chronic; Rheumatoid arthritis; Anticytokine; Interleukin 1; Antagonist; Left ventricle performance; Anakinra
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.107.731877

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. 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). Interleukin-1 inhibition improves vascular and left ventricular function and is associated with reduction of nitrooxidative stress and endothelin.