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The hypercatabolism after massive pediatric burns has been effectively treated with recombinant human growth hormone, an anabolic agent that stimulates protein synthesis and abrogates growth arrest. While experimental studies have shown increased potential for fibrosis induced by growth hormone therapy, adverse effects on human scars have not been investigated. Our aim was to evaluate hypertrophic scar formation in 62 patients randomized to receive injections of 0.05 mg/kg/day of recombinant human growth hormone or placebo, from discharge until 1 year after burn. Scar scales were used to evaluate scar-severity at discharge, 6, 9, 12, and 18-24 months after burn, by three observers blinded to treatment. Computer-assisted planimetry allowed quantification of percentage of hypertrophic scar formation. Types I and III collagens were localized and quantified in scars and normal skin of patients from both groups, using immunohistochemistry with confocal laser microscopy analysis. Insulin-like growth factor-1 blood levels helped assess compliance. Statistical analysis showed that scar hypertrophy significantly increased from 6 to 12 months after injury in both groups, while decreasing at 18-24 months postburn. Types I and III collagens were statistically increased in the reticular layer of scars from both groups when compared to paired normal skin. Insulin-like growth factor-1 was significantly increased in the recombinant human growth factor-treated group. No differences were seen when recombinant human growth factor and control groups were compared using the scar scales, planimetry, or immunohistochemistry. We concluded that recombinant human growth hormone therapy did not adversely affect scar formation and should not contraindicate the administration of recombinant human growth hormone as a therapeutic approach to severely burned children.

Severe burns cause not only skin injury but several marked systemic derangements. During wound healing, matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases play an important role in tissue regeneration and remodeling processes. Therefore, in the present study, we determined the serum levels of MMPs and tissue inhibitor of metalloproteinase-1 in burn patients over time. Serum samples from 12 severely burned children (mean age 7.9 +/- 2.5 years) with >40% total body surface area burns were obtained within 0.5 hours, 3, 7, and 21 days after injury. Pro-MMP-1, MMP-3, MMP-9, and tissue inhibitor of metalloproteinase-1 serum levels were assayed by enzyme-linked immunoassay and compared to normal healthy volunteers. Two-way analysis of variance and Bonferroni's test were used for statistical analysis. Pro-MMP-1 levels in the serum were significantly elevated by the seventh day after burn. MMP-3 and MMP-9 levels showed significant increases by day 3 and 21 compared to normals, respectively. Tissue inhibitor of metalloproteinase-1 levels did not change with time after burn but were significantly higher by 3 days after burn compared to normal serum. In conclusion, changes in MMPs and tissue inhibitor of metalloproteinase-1 occur in burn patients and those changes may be a mechanism beneficial to wound healing.

Children with severe burns benefit from acute therapy with recombinant human growth hormone by maintaining their original stature after injury. This effect is particularly apparent in children injured outside growth-spurt years. [ABSTRACT FROM AUTHOR]