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| Item Type: | Article |
|---|---|
| Title: | Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy |
| Creators Name: | 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. and Fielitz, J. |
| Abstract: | 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. |
| Keywords: | Acute-Phase Reaction, Case-Control Studies, Critical Illness, Gene Expression Regulation, Inflammation, Inflammation Mediators, Interleukin-6, Lipopolysaccharides, Membranes, Muscular Diseases, Oligonucleotide Array Sequence Analysis, Sepsis, Serum Amyloid A Protein, Skeletal Muscle, Tumor Necrosis Factor-alpha, Animals, Mice |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 9 |
| Number: | 3 |
| Page Range: | e92048 |
| Date: | 20 March 2014 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0092048 |
| PubMed: | View item in PubMed |
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