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

George MJ 1 , Jasmin NH 2 , Cummings VT 2 , Richard-Loendt A 3 , Launchbury F 4 , Woollard K 5 Show all authors , Turner-Stokes T 5 , Garcia Diaz AI 5 , Lythgoe M 2 , Stuckey DJ 2 , Hingorani AD 6 , Gilroy DW 1

Affiliations 

  • 1 Department of Clinical Pharmacology, Division of Medicine, University College London, London, United Kingdom
  • 2 Centre for Advanced Biomedical Imaging (CABI), Division of Medicine, University College London, London, United Kingdom
  • 3 Department of Neuropathology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
  • 4 UCL IQPath, Institute of Neurology, University College London, London, United Kingdom
  • 5 Immunology and Inflammation, Faculty of Medicine, Imperial College London, London, United Kingdom
  • 6 Department of Clinical Pharmacology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
JACC Basic Transl Sci, 2021 May;6(5):431-443.
PMID: 34095633 DOI: 10.1016/j.jacbts.2021.01.013

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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