Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction

Overview

Journal JACC Basic Transl Sci

Date 2021 Jun 7

PMID 34095633

Citations 18

Authors

Marc Jonathan George

Nur Hayati Jasmin

Valerie Taylor Cummings

Angela Richard-Loendt

Francesca Launchbury

Kevin Woollard

Tabitha Turner-Stokes

Ana Isabel Garcia Diaz

Mark Lythgoe

Daniel James Stuckey

Aroon Dinesh Hingorani

Derek William Gilroy

Affiliations

Soon will be listed here.

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.

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