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Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice.
Open accessAbstract
The muscles of IL-6 transgenic mice suffer from atrophy. Experiments were carried out on these transgenic mice to elucidate activation of proteolytic systems in the gastrocnemius muscles and blockage of this activation by treatment with the anti-mouse IL-6 receptor (mIL-6R) antibody. Muscle atrophy observed in 16-wk-old transgenic mice was completely blocked by treatment with the mIL-6R antibody. In association with muscle atrophy, enzymatic activities and mRNA levels of cathepsins (B and L) and mRNA levels of ubiquitins (poly- and mono-ubiquitins) increased, whereas the mRNA level of muscle-specific calpain (calpain 3) decreased. All these changes were completely eliminated by treatment with the mIL-6R antibody. This IL-6 receptor antibody could, therefore, be effective against muscle wasting in sepsis and cancer cachexia, where IL-6 plays an important role.
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“the pilot study of Tsujinaka and colleagues showed that transgenic mice chronically overexpressing IL-6 exhibit a marked muscle atrophy [47]; however, the knockout of IL-6 was not sufficient to prevent sarcopenia in a sepsis mouse model [48].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [47]
In the citing paper
“However, it has also been shown that proinflammatory cytokines may inhibit muscle progenitor cell differentiation and that the reactive oxygen species that are produced by M1 cells (nitric oxide) can be cytotoxic if present in sufficient quantities, demonstrating the need for resolution of the proinflammatory response for muscle recovery to proceed beyond this initial stage [120–122].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [122]
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Supportive Care: Cachexia, Anorexia Syndrome
Tisdale, M. J. (2008) · Springer eBooks · doi:10.1007/978-0-387-69252-4_26
Central Nervous System and Innate Immune Mechanisms for Inflammation- and Cancer-induced Anorexia
Ruud, J. (2012) · DiVA (Linkoping University)
Rastreio e diagnóstico genético molecular da doença de Erb nas distrofias musculares das cinturas
Oliveira, A. A. M. D. C. (1999) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/d69y-1b27
PAPEL DO ADRENOCEPTOR BETA 2 NA REGENERAÇÃO MUSCULAR ESQUELÉTICA
Miyabara, E. H. (2014)
Metabolic and Nutritional Complications of Acute Kidney Injury
Siew, E. D., & Himmelfarb, J. (2010) · Elsevier eBooks · doi:10.1016/b978-1-4377-0987-2.00047-9
The aging horse: Effects of inflammation on muscle satellite cells 1,2
Reed, S. A., LaVigne, E. K., Jones, A. K., Patterson, D. F., & Schauer, A. (2015)
Mokarram, N. (2015) · SMARTech Repository (Georgia Institute of Technology)
The relationship between urinary urea nitrogen and CRP after elective aortic surgery
Naruse, S., Mimuro, S., Kato, H., Mizuno, K., Obata, Y., Doi, M., & Sato, S. (2015) · Journal of the Japanese Society of Intensive Care Medicine · doi:10.3918/jsicm.22.265
O’Leary, M. F. (2018) · University of Birmingham Institutional Research Archive (University of Birmingham)
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Alkalamawy, N. (2018) · SVU- International Journal of Veterinary Sciences · doi:10.21608/svu.2018.17935
“IL-6 as a known myogenic factor had 2 distinct effects; under some pathological conditions, IL-6 may lead to muscular atrophy (Tsujinaka et al., 1996) on the other side (at skeletal muscle tissue level) IL-6 may promote the proliferation of satellite cells and their incorporation as new myonuclei…”
BackgroundПАТОФІЗІОЛОГІЧНІ МЕХАНІЗМИ СИНДРОМУ СТІЙКОГО ЗАПАЛЕННЯ, ІМУНОСУПРЕСІЇ І КАТАБОЛІЗМУ
Чуклін, С. М., Chuklin, S. S., & Shershen, G. (2020) · Здобутки клінічної і експериментальної медицини · doi:10.11603/1811-2471.2020.v.i2.11300
Metabolic and Nutritional Complications of Acute Kidney Injury
Siew, E. D., & Liu, K. (2018) · Elsevier eBooks · doi:10.1016/b978-0-323-52978-5.00046-x
Management der rheumatoiden Arthritis beim älteren Patienten
Bauhammer, J. (2023) · Arthritis und Rheuma · doi:10.1055/a-2041-2229
“Da Tumornekrosefaktor(TNF)-alpha und IL-6 eine hemmende Wirkung auf die Muskelproteinsynthese haben, kann dem Therapieprinzip der TNF-alpha- und der IL-6-Hemmung eine mögliche direkte positive Wirkung parallel zur Entzündungshemmung zugesprochen werden [26, 27].”
Background
Metadata
- Authors
- Tsujinaka, T., Fujita, J., Ebisui, C., Yano, M., Kominami, E., Suzuki, K., Tanaka, K., Katsume, A., Ohsugi, Y., Shiozaki, H., & Monden, M.
- Affiliations
- Osaka University Hospital (JP)
- The University of Osaka (JP)
- Juntendo University (JP)
- Institute for Quantitative Biosciences, The University of Tokyo (JP)
- Chugai Pharmaceutical Co., Ltd. (Japan) (JP)
- Venue
- Journal of Clinical Investigation
- Published
- 1996-01-01
- Volume
- 97
- Issue
- 1
- Pages
- 244-249
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507086
- OpenAlex
- W2060757943
- Cited by
- 421
- References
- 57
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 16 · 2023: 10 · 2022: 22 · 2021: 16 · 2020: 13 · 2019: 9 · 2018: 14 · 2017: 11 · 2016: 9 · 2015: 17 · 2014: 9 · 2013: 14 · 2012: 18
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- interleukin-6, IL-6 receptor antibody, muscle atrophy, proteolytic system, cathepsin B, cathepsin L, ubiquitin, CAPN3, gastrocnemius, cancer cachexia, sepsis
- MeSH terms
- Animals, Antibodies, Monoclonal, Body Weight, Calpain, Cathepsin B, Cathepsins, Cysteine Endopeptidases, Humans, Mice, Inbred C57BL, Mice, Transgenic, Multienzyme Complexes, Muscular Atrophy, Organ Size, Endopeptidases, RNA, Messenger, Ubiquitins, Antigens, CD, Interleukin-6, Gene Expression, Rats, Wistar, Receptors, Interleukin, Muscle, Skeletal, Receptors, Interleukin-6, Proteasome Endopeptidase Complex, Mice, Rats, Cathepsin L
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