Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment.
OBJECTIVE
To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children.


BACKGROUND
Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study.


METHODS
Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls.


RESULTS
Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization.


CONCLUSIONS
IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.
Herndon
D N
DN
Department of Surgery, University of Texas Medical Branch and the Shriners Burns Hospital, Galveston 77550, USA.
Ramzy
P I
PI
DebRoy
M A
MA
Zheng
M
M
Ferrando
A A
AA
Chinkes
D L
DL
Barret
J P
JP
Wolfe
R R
RR
Wolf
S E
SE
D002056:Burns / Q000188:drug therapy* / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D015601:Injury Severity Score; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D009132:Muscles / Q000378:metabolism*; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D011506:Proteins; D007334:Insulin-Like Growth Factor I; D005947:Glucose