Growth hormone decreases protein catabolism in children with cystic fibrosis

Despite aggressive nutritional therapy, low body weight and protein catabol ism are common problems in children with cystic fibrosis. Previous studies by our group and others have demonstrated improvement in both height and we ight in children with cystic fibrosis who were treated with human recombina nt GH, and our group has recently documented improved clinical status and l ean tissue mass as well. The purpose of this report is to summarize our fin dings of the effect of GH on whole body protein kinetics in cystic fibrosis and to relate these findings to changes in TNF-alpha levels. We conducted a 1-yr study of 19 prepubertal children with cystic fibrosis ( age 7-12 yr, all <94% of ideal body weight). Ten children were randomly ass igned to take daily injections of GH (0.3 mg/kg-wk), and nine were randomly assigned to be controls. Baseline results from the subjects with cystic fi brosis were compared with results obtained from nine age- and gender-matche d healthy children. Whole body protein turnover was measured at baseline an d every 6 months using the stable isotope [1-C-13]leucine and mass spectrom etric analysis. Leucine rate of appearance, a measure of protein catabolism, was similar in both cystic fibrosis subgroups at baseline and was significantly higher th an in the control children without cystic fibrosis. Treatment with GH resul ted in a significantly lower leucine rate of appearance, as well as signifi cantly lower leucine oxidation. The rate of protein synthesis, as calculate d from these numbers, actually decreased in the cystic fibrosis subgroup. T NF-<alpha> levels were higher in both cystic fibrosis subgroups than in con trols and correlated with leucine rate of appearance. The results of this study suggest that one reason GH improves body weight a nd lean tissue mass is due to improved whole body protein catabolism and im proved efficiency of whole body protein kinetics.