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.
| Original language | English |
|---|---|
| Pages (from-to) | 643-650 |
| Number of pages | 8 |
| Journal | Journal of Clinical Investigation |
| Volume | 99 |
| Issue number | 4 |
| Publication status | Published - Feb 15 1997 |
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Keywords
- growth disorders
- insulin-like growth factor-I
- interleukin 6
- juvenile rheumatoid arthritis
ASJC Scopus subject areas
- Medicine(all)
Cite this
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. / De Benedetti, Fabrizio; Alonzi, Tonino; Moretta, Antonia; Lazzaro, Domenico; Costa, Patrizia; Poli, Valeria; Martini, Alberto; Ciliberto, Gennaro; Fattori, Elena.
In: Journal of Clinical Investigation, Vol. 99, No. 4, 15.02.1997, p. 643-650.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - De Benedetti, Fabrizio
AU - Alonzi, Tonino
AU - Moretta, Antonia
AU - Lazzaro, Domenico
AU - Costa, Patrizia
AU - Poli, Valeria
AU - Martini, Alberto
AU - Ciliberto, Gennaro
AU - Fattori, Elena
PY - 1997/2/15
Y1 - 1997/2/15
N2 - 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.
AB - 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.
KW - growth disorders
KW - insulin-like growth factor-I
KW - interleukin 6
KW - juvenile rheumatoid arthritis
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UR - http://www.scopus.com/inward/citedby.url?scp=0031025204&partnerID=8YFLogxK
M3 - Article
C2 - 9045866
AN - SCOPUS:0031025204
VL - 99
SP - 643
EP - 650
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 4
ER -