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Sepsis induces interleukin 6, gp130/JAK2/STAT3, and muscle wasting

Background Sepsis 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...

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Published in:Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2022-02, Vol.13 (1), p.713-727
Main Authors: Zanders, Lukas, Kny, Melanie, Hahn, Alexander, Schmidt, Sibylle, Wundersitz, Sebastian, Todiras, Mihail, Lahmann, Ines, Bandyopadhyay, Arnab, Wollersheim, Tobias, Kaderali, Lars, Luft, Friedrich C., Birchmeier, Carmen, Weber‐Carstens, Steffen, Fielitz, Jens
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Language:English
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Summary:Background Sepsis 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. Methods We 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. Results Analyses of differentially expressed genes in RNAseq (≥2‐log2‐fold change, P 
ISSN:2190-5991
2190-6009
DOI:10.1002/jcsm.12867