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Cited by 52Cardiac Fibrosis and RemodelingCytokine Signaling Pathways and InteractionsCardiac Ischemia and Reperfusion

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

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George, Marc Jonathan, Jasmin, Nur Hayati, Cummings, Valerie Taylor, Richard-Loendt, Angela, Launchbury, Francesca, Woollard, Kevin, Turner-Stokes, Tabitha, Garcia Diaz, Ana Isabel +4 more·2021·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2021.01.013PMC PMC8165121
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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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  • Animal models have demonstrated the primary role of IL-6 trans-signaling in inflammatory diseases.

    “as evidences from animal models have demonstrated the primary role of IL-6 trans-signaling in inflammatory diseases”

    From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [112]

    The Discussion (page unavailable) concludes that IL-6’s proinflammatory effects after reperfused myocardial infarction are trans-signaling dependent. The introduction also reports reduced atherosclerosis in mice after trans-signaling blockade. These animal-model findings support a role in specific conditions, but not the claim of a primary role across inflammatory diseases generally. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Olamkicept may be more beneficial than global blockade of IL-6.

    “thus may be more beneficial than the global blockade of IL-6 [111, 112].”

    From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [112]

    The Conclusions and Discussion identify Olamkicept as sgp130Fc and suggest that selective IL-6 trans-signaling blockade may be more effective than broader IL-6 blockade. That comparison is made specifically for reperfused myocardial infarction/STEMI; the paper does not establish a general benefit across conditions. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Olamkicept selectively targets sIL-6R but not IL-6 or IL-6R, and can effectively discriminate between IL-6 classic and trans-signaling.

    “olamkicept, selectively targeting sIL-6R but not IL-6 or IL-6R, can effectively discriminate between IL-6 classic and trans-signaling”

    From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [112]

    The Conclusions identify olamkicept as sgp130Fc, and the Results and Discussion show that sgp130Fc blocks trans-signaling without antagonizing free IL-6, distinguishing it from blockade of both classic and trans-signaling. The paper describes its target as the IL-6/sIL-6R complex, however, not sIL-6R alone; it does not establish the claim’s precise receptor-binding distinction. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
George, M. J., Jasmin, N. H., Cummings, V. T., Richard-Loendt, A., Launchbury, F., Woollard, K., Turner-Stokes, T., Garcia Diaz, A. I., Lythgoe, M., Stuckey, D. J., Hingorani, A. D., & Gilroy, D. W.
Affiliations
  • University College London Hospitals NHS Foundation Trust (GB)
  • University College London (GB)
  • UCL Queen Square Institute of Neurology (GB)
  • Imperial College London (GB)
Corresponding author
George, Marc Jonathan
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2021-05
Volume
6
Issue
5
Pages
431-443
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2021.01.013
PMC
PMC8165121
OpenAlex
W3144922262
Cited by
52
References
0
Citations by year
2026: 7 · 2025: 9 · 2024: 13 · 2023: 9 · 2022: 10 · 2021: 4
FWCI
6.03
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UCL Discovery (University College London) (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • Wellcome Trust (108735/Z/15/Z, 212937/Z/18/Z)
  • National Institute for Health Research
  • British Heart Foundation (FS/15/33/31608, RM/17/1/33377)
  • Medical Research Council (MR/R026416/1)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
Keywords
interleukin-6, sgp130Fc, anti-IL-6 antibody, reperfused myocardial infarction, neutrophil infiltration, macrophage infiltration, infarct size, cardiac function, inflammation, anti-inflammatory therapy

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