E-GEOD-53702 - Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy

Status
Released on 6 May 2014, last updated on 12 May 2014
Organism
Homo sapiens
Samples (13)
Array (1)
Protocols (5)
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 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 could be 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. Expression analysis of patients with and without CIM (non-CIM) was performed. Date were quantile normalized using Partek Genomic Suite 6.5, RMA background correction, pre background adjustment for GC content and data were limited to the full dataset
Experiment type
transcription profiling by array 
Contacts
Jens Fielitz <geo@ncbi.nlm.nih.gov>, Steffen Weber-Carstens
Citation
Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy. Langhans C, Weber-Carstens S, Schmidt F, Hamati J, Kny M, Zhu X, Wollersheim T, Koch S, Krebs M, Schulz H, Lodka D, Saar K, Labeit S, Spies C, Hubner N, Spranger J, Spuler S, Boschmann M, Dittmar G, Butler-Browne G, Mouly V, Fielitz J. , Europe PMC 24651840
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-53702.idf.txt
Sample and data relationshipE-GEOD-53702.sdrf.txt
Raw data (2)E-GEOD-53702.raw.1.zip, E-GEOD-53702.raw.2.zip
Processed data (1)E-GEOD-53702.processed.1.zip
Array designA-AFFY-143.adf.txt
Links