Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation.
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Stunted growth is a major complication of chronic inflammation and recurrent infections in children. Systemic juvenile rheumatoid arthritis is a chronic inflammatory disorder characterized by markedly elevated circulating levels of IL-6 and stunted growth. In this study we found that NSE/hIL-6 transgenic mouse lines expressing high levels of circulating IL-6 since early after birth presented a reduced growth rate that led to mice 50-70% the size of nontransgenic littermates. Administration of a monoclonal antibody to the murine IL-6 receptor partially reverted the growth defect. In NSE/hIL-6 transgenic mice, circulating IGF-I levels were significantly lower than those of nontransgenic littermates; on the contrary, the distribution of growth hormone pituitary cells, as well as circulating growth hormone levels, were normal. Treatment of nontransgenic mice of the same strain with IL-6 resulted in a significant decrease in IGF-I levels. Moreover, in patients with systemic juvenile rheumatoid arthritis, circulating IL-6 levels were negatively correlated with IGF-I levels. Our findings suggest that IL-6-mediated decrease in IGF-I production represents a major mechanism by which chronic inflammation affects growth.
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Overexpression of IL-6 causes reduced circulating Igf1 and reduced growth, rescued by anti-IL-6 antibodies.
“The use of mouse models has documented that overexpression of IL-6 causes reduced circulating levels of Igf1 and reduced growth which is rescued by blocking anti-IL-6 antibodies (De Benedetti et al, 1997).”
From Mitochondrial DNA and TLR9 drive muscle inflammation upon Opa1 deficiency (2018) · cites this paper as De Benedetti et al, 1997
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- Authors
- De Benedetti, F., Alonzi, T., Moretta, A., Lazzaro, D., Costa, P., Poli, V, Martini, A., Ciliberto, G., & Fattori, E.
- Affiliations
- Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT)
- University of Pavia (IT)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Venue
- Journal of Clinical Investigation
- Published
- 1997-02-15
- Volume
- 99
- Issue
- 4
- Pages
- 643-650
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507846
- OpenAlex
- W1972763246
- Cited by
- 529
- References
- 48
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 24 · 2018: 23 · 2017: 17 · 2016: 10 · 2015: 31 · 2014: 26 · 2013: 25 · 2012: 24
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- interleukin-6, insulin-like growth factor I, growth arrest, chronic inflammation, systemic juvenile idiopathic arthritis, growth retardation, growth hormone, transgenic mice, child growth
- MeSH terms
- Adolescent, Animals, Arthritis, Juvenile, Blood Glucose, Child, Child, Preschool, Chronic Disease, Disease Models, Animal, Eating, Growth Disorders, Humans, Insulin-Like Growth Factor I, Mice, Inbred C57BL, Mice, Transgenic, Phosphopyruvate Hydratase, Pituitary Gland, Interleukin-6, Mice
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