Τίτλος:
Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fasligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA. © Schattauer 2011.
Συγγραφείς:
Ikonomidis, I.
Tzortzis, S.
Lekakis, J.
Paraskevaidis, I.
Dasou, P.
Parissis, J.
Nikolaou, M.
Markantonis, S.L.
Katsimbri, P.
Skarantavos, G.
Andreadou, I.
Anastasiou-Nana, M.
Περιοδικό:
Thrombosis and Haemostasis
Λέξεις-κλειδιά:
antidiabetic agent; beta adrenergic receptor blocking agent; calcium channel blocking agent; caspase 9; dipeptidyl carboxypeptidase inhibitor; diuretic agent; Fas antigen; Fas ligand; hydroxymethylglutaryl coenzyme A reductase inhibitor; interleukin 1beta; leflunomide; methotrexate; nonsteroid antiinflammatory agent; placebo; prednisolone; recombinant interleukin 1 receptor blocking agent; tumor necrosis factor alpha, adult; apoptosis; article; clinical article; controlled study; crossover procedure; disease association; disease marker; double blind procedure; female; heart disease; heart left ventricle impairment; heart performance; heart stress; human; male; priority journal; protein function; protein modification; randomized controlled trial; rheumatoid arthritis; single drug dose; tissue Doppler imaging; treatment duration; treatment response; two dimensional echocardiography, Adrenal Cortex Hormones; Adult; Aged; Analysis of Variance; Antigens, CD95; Antirheumatic Agents; Apoptosis; Arthritis, Rheumatoid; Biological Markers; Caspase 9; Cross-Over Studies; Double-Blind Method; Echocardiography, Doppler; Fas Ligand Protein; Female; Greece; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Logistic Models; Male; Middle Aged; Myocardium; Prednisolone; Receptors, Interleukin-1; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left
DOI:
10.1160/TH11-02-0117
