Observational studyJournal of cachexia, sarcopenia and muscle2022
Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting.
Observational study in Journal of cachexia, sarcopenia and muscle, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07017517 (Effect of Physical Therapy on NLRP3 Inflammasome Activation and Muscle Atrophy in Critical Illness Myopathy), which is not on this map. Cited by 132 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Physical Therapy on NLRP3 Inflammasome Activation and Muscle Atrophy in Critical Illness Myopathy (PT-NLRP3-CIM).
Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 198 citations in OpenAlex.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- The dual pathogenic role of IL-24 in sepsis: Coupling bacterial dissemination with inflammatory amplification as a therapeutic target.Virulence · 2026Article
- Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.Annals of medicine · 2026Article
- Interleukin-39 is a Prognostic Biomarker and Therapy Target for Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Early Renal Perfusion Scintigraphy Is Associated with Mortality in Experimental Sepsis: A Multimodal Study Integrating Imaging, Survival, and Biomarker Analysis.Diagnostics (Basel, Switzerland) · 2026Article
- Multi-omics Mendelian randomization identified adaptive immune response-related drug targets in psoriatic arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Epigenetic modulation of the JAK2-STAT3 signaling pathway in osteoporosis: non-coding RNA networks as therapeutic targets.Journal of translational medicine · 2026Review
- Muscle Dysfunction in Critical Illness: Established Mechanisms and the Potential Contribution of the NLRP3 Inflammasome.International journal of molecular sciences · 2026Review
- Adenosine 5'-monophosphate prevents sepsis-associated muscle wasting by activating AMPK and suppressing IL-1β inflammatory cytokines.Journal of intensive care · 2026Article
- Piperine attenuates fibrogenesis and inflammation in hepatic fibrosis by switching STAT3 phosphorylation at Ser727.Chinese herbal medicines · 2026Article
- The Prognostic Impact of the Cachexia Index in Patients Hospitalized with Heart Failure.Medicina (Kaunas, Lithuania) · 2026Article
- RIPK3 Inhibition Mitigates Denervated Muscle Atrophy via NOX4-Mediated Mitochondrial Restoration and Inflammation Suppression.Journal of cachexia, sarcopenia and muscle · 2026Article
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Skeletal muscle dysfunction in COPD: miRNAs, myokines and exercise.ERJ open research · 2026Review
- The Conjugated Bile Acids Profile Suggests a Novel Liver-Muscle Axis Associated With Sarcopenia in Chronic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Context-Dependent Regulation of Microglial Metabolic and Immune States via IL-3/CD123 Signaling: Implications for Glial Crosstalk and Cognitive Impairment.Molecular neurobiology · 2026Review
- Skeletal muscle expression of the genes associated with glycoprotein 130 signaling in relation to obesity and insulin sensitivity.Journal of endocrinological investigation · 2026Article
- Parthenolide Attenuates Skeletal Muscle Atrophy Through Regulation of Protein Homeostasis and Inhibition of Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Sarcopenia and body temperature-the significance of interorgan metabolic networks in skeletal muscle atrophy.Endocrine journal · 2026Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSepsis and inflammation can cause intensive care unit-acquired weakness (ICUAW). Increased interleukin-6 (IL-6) plasma levels are a risk factor for ICUAW. IL-6 signalling involves the glycoprotein 130 (gp130) receptor and the JAK/STAT-pathway, but its role in sepsis-induced muscle wasting is uncertain. In a clinical observational study, we found that the IL-6 target gene, SOCS3, was increased in skeletal muscle of ICUAW patients indicative for JAK/STAT-pathway activation. We tested the hypothesis that the IL-6/gp130-pathway mediates ICUAW muscle atrophy.
methodsWe sequenced RNA (RNAseq) from tibialis anterior (TA) muscle of cecal ligation and puncture-operated (CLP) and sham-operated wildtype (WT) mice. The effects of the IL-6/gp130/JAK2/STAT3-pathway were investigated by analysing the atrophy phenotype, gene expression, and protein contents of C2C12 myotubes. Mice lacking Il6st, encoding gp130, in myocytes (cKO) and WT controls, as well as mice treated with the JAK2 inhibitor AG490 or vehicle were exposed to CLP or sham surgery for 24 or 96 h.
resultsAnalyses of differentially expressed genes in RNAseq (≥2-log2-fold change, P < 0.01) revealed an activation of IL-6-signalling and JAK/STAT-signalling pathways in muscle of septic mice, which occurred after 24 h and lasted at least for 96 h during sepsis. IL-6 treatment of C2C12 myotubes induced STAT3 phosphorylation (three-fold, P < 0.01) and Socs3 mRNA expression (3.1-fold, P < 0.01) and caused myotube atrophy. Knockdown of Il6st diminished IL-6-induced STAT3 phosphorylation (-30.0%; P < 0.01), Socs3 mRNA expression, and myotube atrophy. JAK2 (- 29.0%; P < 0.01) or STAT3 inhibition (-38.7%; P < 0.05) decreased IL-6-induced Socs3 mRNA expression. Treatment with either inhibitor attenuated myotube atrophy in response to IL-6. CLP-operated septic mice showed an increased STAT3 phosphorylation and Socs3 mRNA expression in TA muscle, which was reduced in septic Il6st-cKO mice by 67.8% (P < 0.05) and 85.6% (P < 0.001), respectively. CLP caused a loss of TA muscle weight, which was attenuated in Il6st-cKO mice (WT: -22.3%, P < 0.001, cKO: -13.5%, P < 0.001; WT vs. cKO P < 0.001). While loss of Il6st resulted in a reduction of MuRF1 protein contents, Atrogin-1 remained unchanged between septic WT and cKO mice. mRNA expression of Trim63/MuRF1 and Fbxo32/Atrogin-1 were unaltered between CLP-treated WT and cKO mice. AG490 treatment reduced STAT3 phosphorylation (-22.2%, P < 0.05) and attenuated TA muscle atrophy in septic mice (29.6% relative reduction of muscle weight loss, P < 0.05). The reduction in muscle atrophy was accompanied by a reduction in Fbxo32/Atrogin-1-mRNA (-81.3%, P < 0.05) and Trim63/MuRF1-mRNA expression (-77.6%, P < 0.05) and protein content.
conclusionsIL-6 via the gp130/JAK2/STAT3-pathway mediates sepsis-induced muscle atrophy possibly contributing to ICUAW.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.