Acute phase modulation of systemic insulin-like growth factor-1 and its binding proteins after major burn injuries*

OBJECTIVES: To provide a detailed, sequential analysis of insulin-like growth factor-1 and its binding proteins in adults during the acute phase after a major burn injury. DESIGN: Descriptive, repeated measurements for quantitation and characterization of insulin-like growth factor-1 and its binding proteins in adult burn survivors. SETTING: Burn center in a university hospital. PATIENTS: A total of 17 severely burned (>15% total body-surface area burned) adult patients. INTERVENTIONS: Venous blood was collected twice a day for 10 days and centrifuged, and the sera were stored at -80 degrees C until analysis. A series of 340 serum samples were analyzed by radioimmunoassay to determine the circulating concentration of insulin-like growth factor-1 and its major binding proteins (insulin-like growth factor-binding protein), by Western ligand blotting. To better understand the changes seen in systemic insulin-like growth factor-binding protein-3 levels by Western ligand blotting, a proteolysis assay was performed. MEASUREMENTS AND MAIN RESULTS: Insulin-like growth factor-1 levels were reduced from day 0 and correlated with insulin-like growth factor-binding protein-1 and -2 (p <.01), but not insulin-like growth factor-binding protein-3 and -4. Insulin-like growth factor-binding protein-3 was decreased relative to normal on day 0, declined further until day 3, and began recovering by day 6, but returned to only 35% of normal by day 10. Insulin-like growth factor-binding protein-1 and -2 were increased relative to normal and remained increased throughout the 10-day period. Insulin-like growth factor-binding protein-4 concentrations, however, were similar to normal at day 1 but gradually increased over time. Burn serum incubated with recombinant human glycosylated iodine-125 insulin-like growth factor-binding protein-3 did not demonstrate any proteolysis, although proteolysis of nonglycosylated iodine-125 insulin-like growth factor-binding protein-3 reached levels of approximately 40%. CONCLUSIONS: Insulin-like growth factor-binding protein-3 proteolysis does not seem to be the mechanism by which systemic insulin-like growth factor-1 levels are reduced in major burn survivors. In vitro proteolysis of recombinant human glycosylated and nonglycosylated iodine-125 insulin-like growth factor-binding protein-3 does not reflect the in vivo situation in major burn survivors.

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