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September 12, 2026BMC ImmunologyOpen Access

IL-6 trans-signaling inhibition with sgp130Fc protects against sepsis-induced myocardial dysfunction in murine models.

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Why the study?

The specific mechanisms and therapeutic potential of targeting the IL-6 trans-signaling pathway in sepsis-induced myocardial dysfunction remained to be fully elucidated.

Does the selective IL-6 trans-signaling inhibitor sgp130Fc improve cardiac function and mitigate myocardial injury in sepsis-induced myocardial dysfunction?

Population

Septic patients with and without cardiac dysfunction, CLP mice, and LPS-stimulated cardiac cells

Comparison

Selective IL-6 trans-signaling inhibitor sgp130Fc vs controls

Design

Translational study with clinical serum analysis, in vivo murine CLP model, and in vitro experiments

Key result

IL-6 trans-signaling is hyperactivated in sepsis-induced myocardial dysfunction, and targeting this pathway with sgp130Fc provided comprehensive cardioprotection in murine models.

Authors

XLXuefang LiuNYNing YuWTWenbin Tian

Discussion

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Overview

Targeting IL-6 trans-signaling with sgp130Fc provides comprehensive cardioprotection in sepsis-induced myocardial dysfunction by inhibiting the JAK/STAT3 signaling pathway.

Key Points

  • Investigate the role of IL-6 trans-signaling in sepsis-induced myocardial dysfunction (SIMD) and evaluate the cardioprotective efficacy and molecular mechanisms of the selective inhibitor sgp130Fc.
  • Analyzed clinical serum samples from septic patients with and without cardiac dysfunction for inflammatory and cardiac biomarkers.
  • Established a murine model of SIMD using cecal ligation and puncture (CLP), administered sgp130Fc, and assessed cardiac function via echocardiography, histology, and transmission electron microscopy.
  • Cultured LPS-stimulated cardiomyocytes, cardiac fibroblasts, and cardiac microvascular endothelial cells with sgp130Fc and a JAK agonist to determine cellular and molecular mechanisms in vitro and in vivo.
  • Patients with sepsis—especially those with SIMD—displayed significantly elevated serum IL-6, sIL-6R, and cardiac injury biomarkers (cTnI, CK-MB, NT-proBNP), alongside reduced endogenous sgp130.
  • In CLP mice, sgp130Fc administration significantly improved survival and left ventricular function, decreased cardiomyocyte apoptosis and myocardial fibrosis, and preserved mitochondrial ultrastructure.
  • Sgp130Fc attenuated inflammation and protected all three cardiac cell types from LPS-induced injury by inhibiting JAK/STAT3 activation, an effect reversed by pharmacological JAK agonist treatment.

Study Design

Type

Case-Control (n=36)

Multicenter

No

Structured PICO

Does the selective IL-6 trans-signaling inhibitor sgp130Fc improve cardiac function and mitigate myocardial injury in sepsis-induced myocardial dysfunction?

P
Population
36 participants, including 12 with sepsis-induced myocardial dysfunction, 12 with sepsis without cardiac dysfunction, and 12 healthy controls, evaluated for IL-6 trans-signaling biomarkers.
E
Exposure
Selective IL-6 trans-signaling inhibitor, sgp130Fc
O
Outcome
Cardiac function (LVEF and LVFS), survival rates, myocardial injury, apoptosis, fibrosis, and ultrastructural alterationssurrogate

Main Result

Absolute Event Rate: 4.669% vs 0.998%

p-value: p=<0.001

Targeting IL-6 trans-signaling with sgp130Fc provides comprehensive cardioprotection in sepsis-induced myocardial dysfunction by inhibiting the JAK/STAT3 signaling pathway.

Limitations

  • Small clinical sample size (n=24 sepsis patients)
  • Single-center clinical cohort
  • Therapeutic intervention (sgp130Fc) was only evaluated in preclinical animal and in vitro models

Cite This Study

Liu et al. (2026) conducted a case-control in Sepsis-induced myocardial dysfunction (SIMD) (n=36). Sepsis-induced myocardial dysfunction vs. Healthy controls was evaluated on Serum cTnI levels (ng/mL) (p=<0.001). IL-6 trans-signaling is hyperactivated in sepsis-induced myocardial dysfunction, and targeting this pathway with sgp130Fc provided comprehensive cardioprotection in murine models.

synapsesocial.com/papers/6aa55507327956e4761fa089https://doi.org/10.1186/s12865-026-00894-w
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1The interleukin-6/glycoprotein 130 pathway in cardiomyocytes contributes to the pathogenesis of sepsis-induced cardiomyopathy2025
  2. 2IL-6/STAT3 Signaling Promotes Cardiac Dysfunction by Upregulating FUNDC1-Dependent Mitochondria-Associated Endoplasmic Reticulum Membranes Formation in Sepsis Mice2022 · 51 citations
  3. 3Regulation of Inflammatory Responses and Apoptosis: sgp130fc as a Potential Therapeutic Agent for Sepsis-Associated Kidney Injury2026
  4. 4Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction2024 · 1 citations
  5. 5Selective Interleukin-6 Trans-Signaling Blockade Is More Effective Than Panantagonism in Reperfused Myocardial Infarction2021 · 50 citations