title: Burn injury induces high levels of phosphorylated insulin-like growth factor binding protein-1.
abstract: OBJECTIVE
  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.
authors.affiliation: North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina Chapel Hill, NC 27599 USA.
authors.forename: April E
authors.initials: AE
authors.lastname: Mendoza
authors.forename: Laura A
authors.initials: LA
authors.lastname: Maile
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cairns
authors.forename: Robert
authors.initials: R
authors.lastname: Maile
keywords: Insulin-like growth factor; burns; insulin-like growth factor binding protein-1; trauma