Insulinlike growth factor I plus insulinlike growth factor binding protein 3 attenuates the proinflammatory acute phase response in severely burned children

Marc G. Jeschke, Robert E. Barrow, David Herndon

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

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. Summary Background Data. 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, α1-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-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion. Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type 1 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.

Original languageEnglish (US)
Pages (from-to)246-252
Number of pages7
JournalAnnals of Surgery
Volume231
Issue number2
DOIs
StatePublished - Feb 2000

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Acute-Phase Reaction
Insulin-Like Growth Factor I
Fibrinogen
Intercellular Signaling Peptides and Proteins
Carrier Proteins
Acute-Phase Proteins
Liver
Insulin-Like Growth Factor Binding Protein 3
Multiple Organ Failure
Body Surface Area
Interleukin-1
Wounds and Injuries
Tumor Necrosis Factor-alpha
Serum
Retinol-Binding Proteins
Complement C3
Proteins
Prealbumin
Transferrin
Protein C

ASJC Scopus subject areas

  • Surgery

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Insulinlike growth factor I plus insulinlike growth factor binding protein 3 attenuates the proinflammatory acute phase response in severely burned children. / Jeschke, Marc G.; Barrow, Robert E.; Herndon, David.

In: Annals of Surgery, Vol. 231, No. 2, 02.2000, p. 246-252.

Research output: Contribution to journalArticle

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title = "Insulinlike growth factor I plus insulinlike growth factor binding protein 3 attenuates the proinflammatory acute phase response in severely burned children",
abstract = "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. Summary Background Data. 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, α1-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-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion. Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type 1 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.",
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N2 - 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. Summary Background Data. 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, α1-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-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion. Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type 1 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.

AB - 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. Summary Background Data. 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, α1-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-α) and interleukin-1β (IL-1β) levels decreased with IGF-I/BP-3 compared with controls, with no effect on interleukin-6. Conclusion. Severely burned children receiving IGF-I/BP-3 showed a decrease in IL-1β and TNF-α followed by a decrease in type 1 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.

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