Journal
JACC-BASIC TO TRANSLATIONAL SCIENCE
Volume 6, Issue 5, Pages 431-443Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacbts.2021.01.013
Keywords
inflammation; interleukin-6; myocardial infarction; reperfusion
Categories
Funding
- Wellcome Trust [108735/Z/15/Z, 212937/Z/18/Z]
- British Heart Foundation [FS/15/33/31608, RM/17/1/33377]
- Medical Research Council [MR/R026416/1]
- National Institute for Health Research
- King Scholarship of Malaysia
- Wellcome Trust [212937/Z/18/Z, 108735/Z/15/Z] Funding Source: Wellcome Trust
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Interleukin (IL)-6 is an emerging therapeutic target in myocardial infarction (MI), with the novel recombinant fusion protein sgp130Fc showing efficacy in exclusive trans-signaling blockade. In a rat model, sgp130Fc attenuated infiltration and preserved cardiac function, in contrast to anti-IL-6 antibodies that result in panantagonism.
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-inflammatoryeffects. 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. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
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