The IGF system and cytokine interactions and relationships with longitudinal growth in prepubertal patients with cystic fibrosis.
OBJECTIVE
Growth delay is a feature of patients with cystic fibrosis (CF). CF is a condition characterized by chronic inflammation that has been shown to modify the IGF system, which is essential for normal growth, and is related to pulmonary function in CF patients. We aimed to verify whether circulating levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, insulin and the IGF system were related and/or had relationships with linear growth in children with CF.


METHODS
Seventeen prepubertal CF patients (nine males and eight females) in a stable clinical condition were enrolled. Auxological parameters, pulmonary function and the Shwachman-Kulczycki (S-K) score were assessed, and serum samples were drawn at baseline and after 12 months.


METHODS
TNF-alpha, IL-6, IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and insulin were assayed using specific commercial kits.


RESULTS
At baseline, TNF-alpha serum concentration was related to serum IGF-I concentration (R = 0.53), IGF-II bioactivity (IGF-II/IGFBP-3 molar ratio, R = +0.52) and insulin concentration (R = +0.63). Changes in serum IL-6 and IGFBP-2 concentrations during the 12-month observation were positively correlated (R = +0.63). Changes in height standard deviation score (Ht SDS) were correlated with IGF-I serum concentrations at baseline (R =+0.67) and after 12 months (R = +0.70), with IGF-I bioavailability and with IGFBP-1 serum concentrations (R = -0.88). Body mass index (BMI) SDS correlated with IGF bioavailability.


CONCLUSIONS
This study showed a relationship between inflammatory status and the IGF system, and an effect of these interactions on longitudinal growth. Moreover, a role for insulin in growth was identified. Better control of inflammation and preservation of insulin secretion could benefit these patients.
Street
Maria E
ME
Department of Paediatrics, University of Parma, Italy. mariaelisabeth.street@unipr.it
Spaggiari
Cinzia
C
Volta
Cecilia
C
Ziveri
Maria Angela
MA
Viani
Isabella
I
Rossi
Maurizio
M
Pisi
Giovanna
G
Grzincich
GianLuigi
G
Bernasconi
Sergio
S
D016022:Case-Control Studies; D002648:Child; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006128:Growth / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / 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 / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D013002:Somatomedins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D016207:Cytokines; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D015850:Interleukin-6; D013002:Somatomedins; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II