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

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1997 Feb 15

PMID 9045866

Citations 118

Authors

F De Benedetti

T Alonzi

A Moretta

D Lazzaro

P Costa

V Poli

A Martini

G Ciliberto

E Fattori

Affiliations

Soon will be listed here.

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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