IL-6-induced skeletal muscle atrophy
Open accessAbstract
Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling (phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein (−17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase (−60%) and STAT5 (−33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.
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Studies in both animals and humans implicate IL-6 involvement in the repression of protein synthesis.
“studies in both animals and humans implicate IL-6 involvement in the repression of protein synthesis [58, 59].”
From Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis (2018) · cites this paper as [58]
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- Authors
- Haddad, F., Zaldivar, F., Cooper, D. M., & Adams, G. R.
- Affiliations
- University of California, Irvine (US)
- ORCID
- Haddad, F.
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2005-03
- Volume
- 98
- Issue
- 3
- Pages
- 911-917
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2121311831
- Cited by
- 612
- References
- 60
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 39 · 2023: 37 · 2022: 43 · 2021: 34 · 2020: 37 · 2019: 35 · 2018: 40 · 2017: 17 · 2016: 28 · 2015: 43 · 2014: 20 · 2013: 32 · 2012: 26
- FWCI
- 4.26
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Licence
- cc-by
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (5r01ar045594-05)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-45594)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- interleukin-6, skeletal muscle atrophy, myofibrillar protein degradation, RSK, STAT5, STAT3, cytokine signaling, muscle atrophy, muscle catabolism, satellite cells, aging, physical activity
- MeSH terms
- Animals, Female, Muscle Proteins, Muscular Atrophy, Signal Transduction, Interleukin-6, Rats, Sprague-Dawley, Rats
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