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  • Title: Temporal and spatial expression of IGF-I and IGFBP-1 during acute-phase response induced by localized inflammation in rats.
    Author: Novosyadlyy R, Lelbach A, Sheikh N, Tron K, Pannem R, Ramadori G, Scharf JG.
    Journal: Growth Horm IGF Res; 2009 Feb; 19(1):51-60. PubMed ID: 18632293.
    Abstract:
    OBJECTIVE: The acute-phase response (APR), a cytokine-induced defense reaction of the body that enhances the innate immunity mechanisms directed to eliminate the noxious agent and restrict the area of damage, is accompanied by numerous alterations of the IGF axis. The liver is a central organ of both the IGF system and the APR because it releases most of IGF-I and IGFBP-1 in the circulation and is the main target organ for acute-phase-cytokines such as IL-6. METHODS: In the current work the expression of IGF-I and IGFBP-1 was studied in the liver and extrahepatic tissues in a rat model of localized inflammation induced by intramuscular injection of turpentine oil (TO). The mRNA expression of IGF-I and IGFBP-1 was determined by Northern blot analysis and quantitative RT-PCR. Circulating levels of IGF-I and IGFBP-1 were evaluated by radioimmunoassay and [(125)I]-IGF-I ligand blotting, respectively. RESULTS: Administration of TO to the rats led to a significant reduction of IGF-I gene expression in the liver and spleen. These changes were accompanied by a reduction of serum IGF-I concentrations to approximately 50% of levels observed in control rats. In contrast to IGF-I, IGFBP-1 mRNA expression was rapidly elevated in the livers of TO-treated rats. IGFBP-1 transcripts were already detectable at 30 min after TO injection and reached their maximal levels by 6h. IGFBP-1 gene expression was also increased in the kidneys. This elevation, however, was delayed and less prominent than in the liver. CONCLUSIONS: Our data demonstrate that localized inflammation induced by intramuscular TO injection is accompanied not only by decreased IGF-I but also by increased IGFBP-1 gene expression explaining at least in part the catabolic changes of metabolism observed during the acute-phase response.
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