Supervisors info:
Λέκτορας Ιωάννα Ανδρεάδου (επιβλέπουσα), Καθηγητής Παναγιώτης Μαχαίρας, Αναπλ. Καθηγήτρια Σοφία Κυρούδη-Μαρκαντώνη
Summary:
Background: Inhibition of interleukin-1 (IL-1) activity reduces experimental
myocardial infarction by limiting apoptosis. We investigated whether anakinra,
an IL-1 receptor antagonist, reduces apoptosis and thus, improves left
ventricular (LV) function in patients with rheumatoid arthritis (RA).
Methods: We studied 46 RA patients. In an acute, double-blind cross-over trial,
23 patients were randomized to a single injection of anakinra or placebo and
after 48-hours 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-hours and 30-days after treatment, we measured
nitrotyrosine (NT), protein carbonyls, Fas, Fas-ligand and caspase-9 in
circulation to assess nitrooxidative stress and apoptosis. At baseline and
30-days after treatment, we assessed LV longitudinal strain, strain rate and E
to E’ ratio using 2D-speckle tracking and tissue Doppler echocardiography.
Results: At baseline, increased protein carbonyls and NT were related with
increased Fas and Fas-ligand (p<0.05). Increased apoptotic markers were related
with reduced LongSRS and increased E/Em (p<0.05). After 3h 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), protein carbonyls and NT (p<0.05). 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.
Conclusions: Inhibition of IL-1 activity reduces apoptosis through
nitroxidative-stress pathways leading to improved LV function in RA.
Key words: interleukin-1, apoptosis, oxidative stress, myocardial deformation,
anakinra, rheumatoid arthritis
Keywords:
Apoptosis, Anakinra, Oxidative stress, Interleukin-1, Rheumatoid arthritis
