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Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Theme Issue
Immunology of atherosclerosis

DOI: https://doi.org/10.1160/TH11-02-0117
Issue: 2011: 106/5 (Nov) pp. 753-992
Pages: 959-967

Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra

I. Ikonomidis (1), S. Tzortzis (1), J. Lekakis (1), I. Paraskevaidis (1), P. Dasou (2), J. Parissis (1), M. Nikolaou (1), S. L. Markantonis (3), P. Katsimbri (4), G. Skarantavos (4), I. Andreadou (2), M. Anastasiou-Nana (1)

(1) 2nd Cardiology Department, Attikon Hospital, University of Athens, Greece; (2) Department of Pharmaceutical Chemistry, University of Athens School of Pharmacy, Athens, Greece; (3) Laboratory of Biopharmaceutics and Pharmacokinetics, University of Athens School of Pharmacy, Athens, Greece; (4) 1st Department of Orthopaedics, Rheumatology Unit, Attikon Hospital, University of Athens, Greece

Keywords

rheumatoid arthritis, interleukin-1, apoptosis, Anakinra, oxidative stress, myocardial deformation

Summary

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), Fas-ligand (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.

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