Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis.

Abstract

OBJECTIVE:

In inflammatory bowel diseases, increased serum interleukin (IL)-6 levels are associated with high serum insulin-like growth factor-binding protein 2 (IGFBP-2) levels, and cytokines modify the insulin-like growth factor (IGF)/IGFBP system in models in vitro. In cystic fibrosis (CF) the IGF/IGFBP system has not been extensively studied, and relationships with proinflammatory cytokines have not been explored. The aim of this study was to investigate the IGF/IGFBP system and verify changes dependent on IL-1beta, IL-6, tumour necrosis factor alpha (TNFalpha), and insulin.

METHODS:

Eighteen subjects with CF (mean age 26.6 +/- 1.1 years) and 18 controls, comparable for age, sex, and body mass index, were enrolled. Serum IGF-I, IGF-II, IGFBP-2, IGFBP-3, IL-1beta, IL-6, TNFalpha, insulin and C-peptide were measured. Different molecular forms of IGFBP-2 and IGFBP-3 were investigated by Western immunoblotting. The patients were analysed as a whole and as two subgroups depending on established clinical criteria (Swachman-Kulczycki score).

RESULTS:

Patients had higher serum concentrations of IL-1beta, IL-6, TNFalpha and IGFBP-2 than controls. Serum concentrations of IGF-I and IGF-II were significantly lower and insulin and C-peptide levels significantly increased in CF compared with healthy controls whereas IGFBP-3 serum concentrations were similar, with comparable IGF-I/IGFBP-3 and decreased IGF-I/IGFBP-2 and IGF-II/IGFBP-2 molar ratios. From correlation analysis we detected a significant positive correlation between IGFBP-2 and IL-6 and a negative correlation between IGFBP-2 and IGFBP-3.

CONCLUSIONS:

Our findings suggest that inflammation is an important modulator of the IGF/IGFBP system with an overall reduction in IGF bioactivity in CF.

• Authors: Maria E Street, Maria A Ziveri, Cinzia Spaggiari, Isabella Viani, Cecilia Volta, Gian Luigi Grzincich, Raffaele Virdis, Sergio Bernasconi
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 154 Issue 1 Pg. 47-52 (Jan 2006) ISSN: 0804-4643 [Print] England
• PMID: 16381990 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 3
• Interleukin-6
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II

Topics

• Adult
• Cystic Fibrosis (complications, physiopathology)
• Female
• Humans
• Inflammation (complications, physiopathology)
• Insulin (blood)
• Insulin-Like Growth Factor Binding Protein 2 (blood)
• Insulin-Like Growth Factor Binding Protein 3 (blood)
• Insulin-Like Growth Factor I (analysis, physiology)
• Insulin-Like Growth Factor II (analysis, physiology)
• Interleukin-6 (blood)
• Male