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

Fabrizio De Benedetti, Tonino Alonzi, Antonia Moretta, Domenico Lazzaro, Patrizia Costa, Valeria Poli, Alberto Martini, Gennaro Ciliberto, Elena Fattori

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)643-650
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number4
Publication statusPublished - Feb 15 1997

Keywords

  • growth disorders
  • insulin-like growth factor-I
  • interleukin 6
  • juvenile rheumatoid arthritis

ASJC Scopus subject areas

  • Medicine(all)

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