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Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy

OBJECTIVES: Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of the...

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Autores principales: Langhans, Claudia, Weber-Carstens, Steffen, Schmidt, Franziska, Hamati, Jida, Kny, Melanie, Zhu, Xiaoxi, Wollersheim, Tobias, Koch, Susanne, Krebs, Martin, Schulz, Herbert, Lodka, Doerte, Saar, Kathrin, Labeit, Siegfried, Spies, Claudia, Hubner, Norbert, Spranger, Joachim, Spuler, Simone, Boschmann, Michael, Dittmar, Gunnar, Butler-Browne, Gillian, Mouly, Vincent, Fielitz, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961297/
https://www.ncbi.nlm.nih.gov/pubmed/24651840
http://dx.doi.org/10.1371/journal.pone.0092048
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author Langhans, Claudia
Weber-Carstens, Steffen
Schmidt, Franziska
Hamati, Jida
Kny, Melanie
Zhu, Xiaoxi
Wollersheim, Tobias
Koch, Susanne
Krebs, Martin
Schulz, Herbert
Lodka, Doerte
Saar, Kathrin
Labeit, Siegfried
Spies, Claudia
Hubner, Norbert
Spranger, Joachim
Spuler, Simone
Boschmann, Michael
Dittmar, Gunnar
Butler-Browne, Gillian
Mouly, Vincent
Fielitz, Jens
author_facet Langhans, Claudia
Weber-Carstens, Steffen
Schmidt, Franziska
Hamati, Jida
Kny, Melanie
Zhu, Xiaoxi
Wollersheim, Tobias
Koch, Susanne
Krebs, Martin
Schulz, Herbert
Lodka, Doerte
Saar, Kathrin
Labeit, Siegfried
Spies, Claudia
Hubner, Norbert
Spranger, Joachim
Spuler, Simone
Boschmann, Michael
Dittmar, Gunnar
Butler-Browne, Gillian
Mouly, Vincent
Fielitz, Jens
author_sort Langhans, Claudia
collection PubMed
description OBJECTIVES: Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM. DESIGN: Prospective observational clinical study and prospective animal trial. SETTING: Two intensive care units (ICU) and research laboratory. PATIENTS/SUBJECTS: 33 patients with Sequential Organ Failure Assessment scores ≥8 on 3 consecutive days within 5 days in ICU were investigated. A subgroup analysis of 12 patients with, and 18 patients without CIM (non-CIM) was performed. Two consecutive biopsies from vastus lateralis were obtained at median days 5 and 15, early and late time points. Controls were 5 healthy subjects undergoing elective orthopedic surgery. A septic mouse model and cultured myoblasts were used for mechanistic analyses. MEASUREMENTS AND MAIN RESULTS: Early SAA1 expression was significantly higher in skeletal muscle of CIM compared to non-CIM patients. Immunohistochemistry showed SAA1 accumulations in muscle of CIM patients at the early time point, which resolved later. SAA1 expression was induced by IL-6 and tumor necrosis factor-alpha in human and mouse myocytes in vitro. Inflammation-induced muscular SAA1 accumulation was reproduced in a sepsis mouse model. CONCLUSIONS: Skeletal muscle contributes to general inflammation and acute-phase response in CIM patients. Muscular SAA1 could be important for CIM pathogenesis. TRIAL REGISTRATION: ISRCTN77569430.
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spelling pubmed-39612972014-03-27 Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy Langhans, Claudia Weber-Carstens, Steffen Schmidt, Franziska Hamati, Jida Kny, Melanie Zhu, Xiaoxi Wollersheim, Tobias Koch, Susanne Krebs, Martin Schulz, Herbert Lodka, Doerte Saar, Kathrin Labeit, Siegfried Spies, Claudia Hubner, Norbert Spranger, Joachim Spuler, Simone Boschmann, Michael Dittmar, Gunnar Butler-Browne, Gillian Mouly, Vincent Fielitz, Jens PLoS One Research Article OBJECTIVES: Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM. DESIGN: Prospective observational clinical study and prospective animal trial. SETTING: Two intensive care units (ICU) and research laboratory. PATIENTS/SUBJECTS: 33 patients with Sequential Organ Failure Assessment scores ≥8 on 3 consecutive days within 5 days in ICU were investigated. A subgroup analysis of 12 patients with, and 18 patients without CIM (non-CIM) was performed. Two consecutive biopsies from vastus lateralis were obtained at median days 5 and 15, early and late time points. Controls were 5 healthy subjects undergoing elective orthopedic surgery. A septic mouse model and cultured myoblasts were used for mechanistic analyses. MEASUREMENTS AND MAIN RESULTS: Early SAA1 expression was significantly higher in skeletal muscle of CIM compared to non-CIM patients. Immunohistochemistry showed SAA1 accumulations in muscle of CIM patients at the early time point, which resolved later. SAA1 expression was induced by IL-6 and tumor necrosis factor-alpha in human and mouse myocytes in vitro. Inflammation-induced muscular SAA1 accumulation was reproduced in a sepsis mouse model. CONCLUSIONS: Skeletal muscle contributes to general inflammation and acute-phase response in CIM patients. Muscular SAA1 could be important for CIM pathogenesis. TRIAL REGISTRATION: ISRCTN77569430. Public Library of Science 2014-03-20 /pmc/articles/PMC3961297/ /pubmed/24651840 http://dx.doi.org/10.1371/journal.pone.0092048 Text en © 2014 Langhans et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Langhans, Claudia
Weber-Carstens, Steffen
Schmidt, Franziska
Hamati, Jida
Kny, Melanie
Zhu, Xiaoxi
Wollersheim, Tobias
Koch, Susanne
Krebs, Martin
Schulz, Herbert
Lodka, Doerte
Saar, Kathrin
Labeit, Siegfried
Spies, Claudia
Hubner, Norbert
Spranger, Joachim
Spuler, Simone
Boschmann, Michael
Dittmar, Gunnar
Butler-Browne, Gillian
Mouly, Vincent
Fielitz, Jens
Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title_full Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title_fullStr Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title_full_unstemmed Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title_short Inflammation-Induced Acute Phase Response in Skeletal Muscle and Critical Illness Myopathy
title_sort inflammation-induced acute phase response in skeletal muscle and critical illness myopathy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961297/
https://www.ncbi.nlm.nih.gov/pubmed/24651840
http://dx.doi.org/10.1371/journal.pone.0092048
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