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

Street, Maria Elisabeth; Ziveri, M.; Spaggiari, Cinzia; Viani, Isabella; Volta, C.; Grzincich, G.L.; Virdis, R; Bernasconi, Sergio

doi:10.1530/eje.1.02064

Cited by 60 publications

(67 citation statements)

References 34 publications

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“…We showed that in inflammatory bowel diseases in relapse, serum IL-6 and IGFBP-2 were increased and positively correlated (17). We also observed similar relationships in patients with cystic fibrosis, suggesting reduced IGF bioactivity (18). In caco-2 cells, we showed that both IL-1 and IL-6 reduced IGFBPs-2 and -4 concentrations (19).…”

Section: Introductionsupporting

confidence: 79%

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Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

et al. 2006

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Objectives: The IGF system is central to fetal growth. Recently, the relationships between cytokines and the IGF system have been shown in specific tissues. It is unknown whether these occur in the placenta. The aim of this study was to assess whether interleukin-6 (IL-6) modulated the IGF system. Methods: Whole villous tissue and cord serum were collected from fetal growth restriction (FGR) neonates diagnosed before birth with altered Doppler velocimetry and controls. Sixteen FGR and 20 controls, born after week 32 of gestation from elective Caesarean sections, were compared. Total RNA was extracted from the placenta samples, reverse transcribed, and real-time quantitative reverse transcriptase (RT)-PCR was performed to quantify cDNA for IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-2, and IL-6. The same proteins were assayed in placenta lysates and cord serum using specific commercial kits and western immunoblotting. Results: FGR subjects had significantly more IGFBPs-1 and -2, and IL-6 mRNA and corresponding proteins in the placenta. In particular, the less phosphorylated isoforms of IGFBP-1 were highly increased. IL-6 and IGFBPs-2 mRNA, and IL-6 and IGFBP-1 peptides were positively and significantly correlated in the placenta. The IGF-II peptide was also significantly increased in FGR placentas. In cord serum, IGFBPs-1 and -2 were significantly more elevated in the FGR neonates. Serum IL-6 was significantly and positively correlated with both IGFBP-1 and IGFBP-2. Conclusions: The placenta of FGR neonates has higher IGF-II, IGFBP-1, IGFBP-2, and IL-6 contents compared with controls. At birth, IGFBPs-1 and -2 are increased in the cord blood of FGR neonates. IL-6 and IGFBP-2 gene expressions are closely related in the placenta. We suggest that the increase in IL-6 and IGFBP-2 could be subsequent to hypoxia and nutrient deficiency. As IGFBP-2 has a strong affinity for IGF-II, which is crucial for fetal growth, it could be an important bioregulator of IGF-II in the placenta.European Journal of Endocrinology 155 567-574

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Section: Introductionsupporting

confidence: 79%

“…We detected similar relationships in the corresponding serum proteins in inflammatory bowel diseases and cystic fibrosis patients. These findings suggested that IGFBP-2 reacted as an acute phase protein (17,18). Possibly, IL-6 regulates IGFBP-2 gene expression or there is a common factor upregulating both genes.…”

Section: Discussionmentioning

confidence: 99%

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

et al. 2006

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“…The mechanism subserving this link is presently not known. Recent data suggest that inflammatory mediators may play a role in inducing reduced IGF-I bioactivity (90) and in recent years adipose tissue has emerged as an important source of pro-inflammatory mediators (51). The question of whether these mediators play a role in the IGF-I/IGF-binding protein system in obesity requires future study.…”

Section: The Gh-insulin-like-growth-factor-i (Igf-i) Axis In Obesitymentioning

confidence: 99%

Obesity, growth hormone and weight loss

Rasmussen

2010

Molecular and Cellular Endocrinology

105

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Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.

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“…Alguns autores sugerem condição de resistência ao GH nos pacientes com FC (30). O aumento das citoquinas pró-inflamatórias na doença levaria à diminuição na produção hepática de IGF-1, além de diminuir a bioatividade do IGF-1 circulante (31,32). Hardin e cols.…”

Section: Segurança Do Tratamento Com Ghunclassified

Tratamento com hormônio de crescimento em crianças com doenças crônicas

Barreto

Bigolin

Ramos

et al. 2008

Arq Bras Endocrinol Metab

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Crianças com doenças crônicas freqüentemente apresentam crescimento inadequado e baixa estatura. A falência do crescimento é multifatorial. Nas doenças inflamatórias, como na artrite juvenil idiopática e nas doenças inflamatórias intestinais, o crescimento é comprometido também pelo processo inflamatório. Muitas vezes, o tratamento da doença de base compromete o crescimento, especialmente quando é necessário glicocorticóides. Em algumas situações é possível comprovar a deficiência associada de hormônio de crescimento (GH, do inglês growth hormone). Em outras, os exames sugerem certo grau de insensibilidade ao GH. O tratamento destes pacientes com GH tem se mostrado útil e seguro com melhora do crescimento e da qualidade de vida. Nesta revisão, são apresentados resultados do tratamento com GH em pacientes com baixa estatura decorrente de doenças crônicas, algumas indicações já bem definidas e outras ainda em investigação.

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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

Cited by 60 publications

References 34 publications

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

Changes in interleukin-6 and IGF system and their relationships in placenta and cord blood in newborns with fetal growth restriction compared with controls

Obesity, growth hormone and weight loss

Tratamento com hormônio de crescimento em crianças com doenças crônicas

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