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A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
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Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused

Marc Jonathan George1,2, Nur Hayati Jasmin3, Valerie Taylor Cummings3

  • 1Department of Clinical Pharmacology, Division of Medicine, University College London, London, United Kingdom.

JACC. Basic to Translational Science
|June 7, 2021
PubMed

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.

Keywords:
AAR, area at riskAb, antibodyCCL, C-C motif chemokine ligandCMR, cardiac magnetic resonanceCXCL, C-X-C motif ligandICAM-1, intercellular adhesion molecule 1IL, interleukinIS, infarct sizeLGE, late-gadolinium enhancementLVEF, left ventricular ejection fractionMHC, major histocompatibility complexMI, myocardial infarctionNSTEMI, non–ST-segment-elevation MIRCAEC, rat coronary artery endothelial cellSTEMI, ST-segment-elevation MITCZ, tocilizumabTrop-T, troponin Tc-caspase-3, cleaved caspase-3inflammationinterleukin-6myocardial infarctionreperfusionsIL-6R, soluble IL-6 receptor

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