title: 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.affiliation: Department of Paediatrics, University of Parma, Via Gramsci, 14, 43100 Parma, Italy. mariaelisabeth.street@unipr.it
authors.forename: Maria E
authors.initials: ME
authors.lastname: Street
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ziveri
authors.forename: Cinzia
authors.initials: C
authors.lastname: Spaggiari
authors.forename: Isabella
authors.initials: I
authors.lastname: Viani
authors.forename: Cecilia
authors.initials: C
authors.lastname: Volta
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Grzincich
authors.forename: Raffaele
authors.initials: R
authors.lastname: Virdis
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernasconi
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000502:physiology*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000502:physiology*; D015850:Interleukin-6 / Q000097:blood; D008297:Male
chemical_list: D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II