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

Department of Paediatrics, University of Parma, Via Gramsci, 14, 43100 Parma, Italy

(Correspondence should be addressed to M E Street; Email: mariaelisabeth.street{at}unipr.it)

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-1ß, IL-6, tumour necrosis factor (TNF), 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-1ß, IL-6, TNF, 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-1ß, IL-6, TNF 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.

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				M. E Street, P. Seghini, S. Fieni, M. A. Ziveri, C. Volta, D. Martorana, I. Viani, D. Gramellini, and S. Bernasconi Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls. Eur. J. Endocrinol., October 1, 2006; 155(4): 567 - 574. [Abstract] [Full Text] [PDF]