Insulinlike growth factor I plus insulinlike growth factor binding protein 3 attenuates the proinflammatory acute phase response in severely burned children.
OBJECTIVE
To determine the effect of insulinlike growth factor I (IGF-I) in combination with its principal binding protein (IGFBP-3) on the hepatic acute phase response in severely burned children.


BACKGROUND
The hepatic acute phase response is a cascade of events initiated to restore homeostasis after trauma. A prolonged response, however, may contribute to multiple organ failure, hypermetabolism, complications, and death.


METHODS
Twenty-two children with a mean total body surface area (TBSA) burn of 57 +/- 3% were given a continuous infusion of 1 to 4 mg/kg/day IGF-I/BP-3 for 5 days after wound excision and grafting. Eight children with a TBSA burn of 54 +/- 4% were given saline as controls. Before and 5 days after excision and grafting, blood samples were taken for serum hepatic constitutive protein, acute phase protein, and proinflammatory cytokine analysis.


RESULTS
Serum IGF-I levels in burned children given the IGF-I/BP-3 complex increased from 113 +/- 15 to 458 +/- 40 ng/mL and IGFBP-3 levels increased from 1.8 +/- 0.2 to 3.1 +/- 0.3 ng/mL. Levels of serum constitutive hepatic proteins (prealbumin, retinol-binding protein, and transferrin) increased with IGF-I/BP-3, whereas levels of type I acute phase proteins (C-reactive protein, alpha1-acid glycoprotein, and complement C-3) decreased when compared with controls. The complex had no effect on type II acute phase proteins. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6.


CONCLUSIONS
Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1beta and TNF-alpha followed by a decrease in type I acute phase proteins that was associated with a concomitant increase in constitutive hepatic proteins. Attenuating the proinflammatory acute phase with IGF-1/BP-3 response may prevent multiple organ failure and improve clinical outcomes after thermal injury without any detectable adverse side effects.
Jeschke
M G
MG
Shriners Hospital for Children and the Department of Surgery, University of Texas Medical Branch, Galveston 77550, USA.
Barrow
R E
RE
Herndon
D N
DN
D000210:Acute-Phase Reaction / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D002056:Burns / Q000097:blood / Q000150:complications*; D002648:Child; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008099:Liver / Q000503:physiopathology; D008297:Male; D009102:Multiple Organ Failure / Q000517:prevention & control; D011994:Recombinant Proteins / Q000627:therapeutic use
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I