title: Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Prospective observational clinical study and prospective animal trial.
  
  
  METHODS
  Two intensive care units (ICU) and research laboratory.
  
  
  METHODS
  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.
  
  
  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.
  
  
  BACKGROUND
  ISRCTN77569430.
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Langhans
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Weber-Carstens
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Jida
authors.initials: J
authors.lastname: Hamati
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Kny
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Wollersheim
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Koch
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Krebs
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Schulz
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Doerte
authors.initials: D
authors.lastname: Lodka
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Saar
authors.affiliation: Universitätsmedizin Mannheim, Mannheim, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Labeit
authors.affiliation: Charité Universitätsmedizin Berlin, Campus Virchow and Campus Mitte, Anesthesiology and Operative Intensive Care Medicine, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Spies
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hubner
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany; Charité Universitätsmedizin Berlin, NeuroCure Clinical Research Center, Berlin, Germany; Charité Universitätsmedizin Berlin, Department of Endocrinology, Diabetes and Nutrition, Berlin, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Spranger
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Spuler
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Boschmann
authors.affiliation: Max Delbrück Center for Molecular Medicine, Berlin, Germany.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Dittmar
authors.affiliation: Institut de Myologie, Institut national de la santé et de la recherche médicale, and L'Université Pierre et Marie Curie Paris, Paris, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Butler-Browne
authors.affiliation: Institut de Myologie, Institut national de la santé et de la recherche médicale, and L'Université Pierre et Marie Curie Paris, Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Mouly
authors.affiliation: Experimental and Clinical Research Center (ECRC), a Cooperation between Max Delbrück Center and Charité Universitätsmedizin Berlin, Campus Buch, Berlin, Germany; Charité Universitätsmedizin Berlin, Campus Virchow, Cardiology, Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fielitz
mesh_terms: D000210:Acute-Phase Reaction / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D016638:Critical Illness; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000187:drug effects; D051379:Mice; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D009135:Muscular Diseases / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D018805:Sepsis / Q000150:complications / Q000473:pathology; D000685:Serum Amyloid A Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; C521404:SAA1 protein, human; C094771:SAA4 protein, human; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha