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-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.
Street
Maria E
ME
Department of Paediatrics, University of Parma, Via Gramsci, 14, 43100 Parma, Italy. mariaelisabeth.street@unipr.it
Ziveri
Maria A
MA
Spaggiari
Cinzia
C
Viani
Isabella
I
Volta
Cecilia
C
Grzincich
Gian Luigi
GL
Virdis
Raffaele
R
Bernasconi
Sergio
S
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
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