Cited by 529Growth Hormone and Insulin-like Growth FactorsCytokine Signaling Pathways and InteractionsAutoimmune and Inflammatory Disorders Research

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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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De Benedetti, F, Alonzi, T, Moretta, A, Lazzaro, D, Costa, P, Poli, V, Martini, A, Ciliberto, G, Fattori, E·1997·Journal of Clinical Investigation

DOI 10.1172/jci119207PMC PMC507846

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Abstract

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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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)
ORCID: Alonzi, T
Moretta, A
Poli, V
Martini, A
Ciliberto, G
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-02-15
Volume: 99
Issue: 4
Pages: 643-650
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119207
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
Life Sciences › Immunology and Microbiology › Immunology › 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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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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