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

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