Insulinlike growth factor I plus insulinlike growth factor binding protein3 attenuates the proinflammatory acute phase response in severely burned children

Objective To determine the effect of insulinlike growth factor I (IGF-I) in combinati on with its principal binding protein (IGFBP-3) on the hepatic acute phase response in severely burned children. Summary Background Data The hepatic acute phase response is a cascade of events initialed to restor e homeostasis after trauma. A prolonged response, however, may contribute t o 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 prote in, acute phase protein, and proinflammatory cytokine analysis. Results Ser um IGF-I levels in burned children given the IGF-I/BP-3 complex increased f rom 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/ BP3, whereas levels of type I acute phase proteins (C-reactive protein, alp ha(1)-acid glycoprotein, and complement C-3) decreased when compared with c ontrols. The complex had no effect on type II acute phase proteins. Tumor n ecrosis factor-alpha TNF-alpha and interleukin-1 beta (IL-1 beta) levels de creased with IGF-I/BP-3 compared with controls, with no effect on interleuk in-6. Conclusion Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1 bet a 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-I/BP-3 response may prevent multiple organ failure and improve clinical outcomes after thermal injury without any detectable adverse side effects.