Selective interleukin-6 trans-signaling blockade is more effective than panantagonism in reperfused myocardial infarction
Author(s)
George, Marc Jonathan
Jasmin, Nur Hayati
Cummings, Valerie Taylor
Richard-Loendt, Angela
Launchbury, Francesca
Type
Journal Article
Abstract
Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI). IL-6 has 2 distinct signaling pathways: trans-signaling, which mediates inflammation, and classic signaling, which also has anti-inflammatory effects. The novel recombinant fusion protein sgp130Fc achieves exclusive trans-signaling blockade, whereas anti-IL-6 antibodies (Abs) result in panantagonism. In a rat model of reperfused MI, sgp130Fc, but not anti-IL-6-Ab, attenuated neutrophil and macrophage infiltration into the myocardium, reduced infarct size, and preserved cardiac function 28 days after MI. These data demonstrate the efficacy of exclusive IL-6 trans-signaling blockade and support further investigation of sgp130Fc as a potential novel therapy in MI.
Date Issued
2021-05-01
Date Acceptance
2021-01-25
Citation
JACC: Basic to Translational Science, 2021, 6 (5), pp.431-443
ISSN
2452-302X
Publisher
Elsevier
Start Page
431
End Page
443
Journal / Book Title
JACC: Basic to Translational Science
Volume
6
Issue
5
Copyright Statement
©2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC by license (http://creativecommons.org/licenses/by/4.0/)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34095633
PII: S2452-302X(21)00068-1
Subjects
AAR, area at risk
Ab, antibody
CCL, C-C motif chemokine ligand
CMR, cardiac magnetic resonance
CXCL, C-X-C motif ligand
ICAM-1, intercellular adhesion molecule 1
IL, interleukin
IS, infarct size
LGE, late-gadolinium enhancement
LVEF, left ventricular ejection fraction
MHC, major histocompatibility complex
MI, myocardial infarction
NSTEMI, non–ST-segment-elevation MI
RCAEC, rat coronary artery endothelial cell
STEMI, ST-segment-elevation MI
TCZ, tocilizumab
Trop-T, troponin T
c-caspase-3, cleaved caspase-3
inflammation
interleukin-6
myocardial infarction
reperfusion
sIL-6R, soluble IL-6 receptor
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2021-04-07