Differential effects of inhibition of interleukin 1 and 6 on myocardial, coronary and vascular function

  • Ignatios IkonomidisEmail author
  • George Pavlidis
  • Pelagia Katsimbri
  • Ioanna Andreadou
  • Helen Triantafyllidi
  • Maria Tsoumani
  • Maria Varoudi
  • Dimitrios Vlastos
  • George Makavos
  • Gavriella Kostelli
  • Dimitrios Βenas
  • John Lekakis
  • John Parissis
  • Dimitrios Boumpas
  • Dimitrios Alexopoulos
  • Efstathios Iliodromitis
Original Paper



Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis.


120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3 months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment.


At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (− 16% vs. − 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5 µM/L), protein carbonyls (0.0132 vs. 0.0115 nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p < 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2 m/s p < 0.05 for all comparisons).


Anakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function.

Clinical Trial Registration

URL: https:// Unique identifier: NCT03288584.


Interleukin 1 Interleukin 6 Rheumatoid arthritis Myocardial deformation Pulse wave velocity Coronary flow reserve 



This work was supported by Grants from the Hellenic Society of Cardiology and Hellenic Society of Lipidiology and Atherosclerosis have supported the study by a grant.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

392_2019_1443_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 KB)
392_2019_1443_MOESM2_ESM.docx (16 kb)
Supplementary material 2 (DOCX 16 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Ignatios Ikonomidis
    • 1
    Email author
  • George Pavlidis
    • 1
  • Pelagia Katsimbri
    • 2
  • Ioanna Andreadou
    • 3
  • Helen Triantafyllidi
    • 1
  • Maria Tsoumani
    • 3
  • Maria Varoudi
    • 1
  • Dimitrios Vlastos
    • 1
  • George Makavos
    • 1
  • Gavriella Kostelli
    • 1
  • Dimitrios Βenas
    • 1
  • John Lekakis
    • 1
  • John Parissis
    • 1
  • Dimitrios Boumpas
    • 2
  • Dimitrios Alexopoulos
    • 1
  • Efstathios Iliodromitis
    • 1
  1. 1.2nd Department of Cardiology, Medical School, Attikon HospitalNational and Kapodistrian University of AthensAthensGreece
  2. 2.4th Department of Internal Medicine, Medical School, Attikon HospitalNational and Kapodistrian University of AthensAthensGreece
  3. 3.Department of Pharmaceutical Chemistry, School of PharmacyNational and Kapodistrian University of AthensAthensGreece

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