title: Inhibition of interleukin-1 by anakinra improves vascular and left ventricular function in patients with rheumatoid arthritis.
abstract: 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.
  
  
  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.affiliation: 2nd Department of Cardiology, University of Athens, Attikon Hospital, Athens, Greece. ignoik@otenet.gr
authors.forename: Ignatios
authors.initials: I
authors.lastname: Ikonomidis
authors.forename: John P
authors.initials: JP
authors.lastname: Lekakis
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolaou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Paraskevaidis
authors.forename: Ioanna
authors.initials: I
authors.lastname: Andreadou
authors.forename: Theophania
authors.initials: T
authors.lastname: Kaplanoglou
authors.forename: Pelagia
authors.initials: P
authors.lastname: Katsimbri
authors.forename: Grigorios
authors.initials: G
authors.lastname: Skarantavos
authors.forename: Panayiotis N
authors.initials: PN
authors.lastname: Soucacos
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001808:Blood Vessels / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D016232:Endothelins; D005260:Female; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000008:administration & dosage* / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide; D018384:Oxidative Stress / Q000187:drug effects; D011994:Recombinant Proteins; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D016232:Endothelins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011994:Recombinant Proteins; D009569:Nitric Oxide