Highlights
- •IL-1 bioactivity is regulated at several levels including by soluble receptors.
- •Levels of soluble regulators of IL-1 activity are changed in patients with STEMI.
- •Soluble IL-1 receptor 2 (sIL-1R2) remain elevated in the acute and chronic phase.
- •Levels of sIL-1R2 are strongly associated with development of LV remodelling.
- •sIL-1R2 levels associate with remodelling after adjustment for clinical covariates.
Abstract
Background
The inflammatory response following myocardial infarction (MI) is prerequisite for
proper healing of infarcted tissue, but can also have detrimental effects on cardiac
function. Interleukin (IL)-1α and IL-1β are potent inflammatory mediators and their
bioactivity is tightly regulated by IL-1 receptor antagonist (IL-1ra) and soluble
(s) IL-1 receptors (R). We aimed to examine whether levels of soluble regulators of
IL-1 signalling are changed during ST-elevation MI (STEMI) and their associations
with parameters of cardiac injury and ventricular remodelling.
Methods
Plasma levels of IL-1Ra, sIL-1R1, sIL-1R2 and sIL-1R accessory protein (sIL-1RAcP)
were measured by immunoassays in repeated samples from patients with STEMI (n = 255) and compared to healthy controls (n = 65).
Results
IL-1Ra, sIL-1R1 and sIL-1R2 levels were all significantly elevated after STEMI, while
levels of sIL-1RAcP were lower compared to controls. sIL-1R2 levels (at different
time points) correlated positively with C-reactive protein, myocardial infarct size
and change in indexed left ventricular end-diastolic and end-systolic volume (LVEDVi
and LVESVi) measured by cardiac MR acutely and after 4 months, and negatively with
LV ejection fraction. Patients with >median levels of sIL-1R2 in the acute phase were
more likely to have increased change in LVEDVi and LVESVi. Importantly, sIL-1R2 remained
significantly associated with change in LVEDVi and LVESVi also after adjustment for
clinical covariates.
Conclusion
Levels of sIL-1R2 are independently associated with parameters of LV adverse remodelling
following STEMI.
Keywords
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Article info
Publication history
Published online: May 11, 2018
Accepted:
May 10,
2018
Received in revised form:
April 24,
2018
Received:
February 16,
2018
Footnotes
☆This work was supported by grants from Helse Sør-Øst Regional Health Authority, Norway [grant number 2012037 to A.Y.]; Norwegian Research Council [grant number 240099/F20 to P.A.]; and the European Community's Seventh Framework Programme [grant number 602699 to T.E.M.]. The study was also supported by The Norwegian Council on Cardiovascular Disease, The Odd Fellow Foundation and The Simon Fougner Hartmann Family Fund. Funding sources had no involvement in study design, analysis/study design, or in writing of the manuscript. There are no conflicts of interest to declare.
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