Burn injury induces high levels of phosphorylated insulin-like growth factor binding protein-1

[摘要] Purpose: Burn injury is associated with early apoptotic death of T cells. Insulin-like growth factor-1 (IGF-I) is able to protect T cells from apoptosis. Association of IGF-I with its IGFBP (Binding Protein)-1 limits its bioavailability and serine phosphorylation of IGFBP-1 lowers this further because of an increased affinity for IGF-I. The level of phosphorylated IGFBP-1 has been shown to increase in pediatric burn patients. Thus we hypothesized that a longitudinal study of burn patients would demonstrate 1) increased IGFBP-1 levels, 2) increased IGFBP-1 phosphorylation and 3) decreased IGF-I levels over time. Methods: We conducted a prospective observational study in adult burn patients admitted to UNC Jaycee Burn Center. Plasma levels of insulin, insulin-like growth factor 1 (IGF-I) and insulin-like growth factor binding protein 1 (IGGBP-1) were measured on admission up to 10 days post admission. ELISA was used to measure serum levels of insulin, IGF-I and IGFBP-1. Serine phosphorylation of IGFBP-1 was measured by Western blot with and without the incubation of calf intestinal phosphatase (CIP). Significant findings: There was a significant positive correlation of increasing %TBSA burn and increasing levels of serum IGFBP-1 from admittance blood draws. Levels of IGF-I also decreased with increasing Total Body Surface Area (TBSA, p<0.05). In patients studied longitudinally (n=84) we found that IGFBP-1 levels are significantly (p<0.05) increased 1-72 hours post burn (mean±SEM serum concentration; burn=172±23 ng/mL, normal=13±3 ng/mL) and that levels of IGF-I are reduced. IGFBP-1 is serine phosphorylated in burn patients. In patients surviving past 72 hours IGFBP-1 remained phosphorylated over the study period. Conclusions: IGFBP-1 and its serine phosphorylation regulate and limit IGF-I bioavailability. Our results suggest that increases in IGFBP-1 and persistent serine phosphorylation of IGFBP-1 correlate with the severity of burn injury, and may contribute to burn-associated T cell apoptosis and subsequent immune dysfunction by reducing the bioavailability of this important cell survival factor.

[学科分类] 外科医学

[关键词] Insulin-like growth factor;insulin-like growth factor binding protein-1;trauma;burns