Serum cytokine levels in GH-deficient children during substitutive GH therapy

Objective: The aim of the present study was to investigate the effect of exogenously administered human GH (hGH) on serum levels of interleukin (IL)-4, IL-6, IL-12 and tumour necrosis factor (TNF)-alpha in GH-deficient (GHD) children. Design and methods: We evaluated 13 short prepubertal GHD children, aged between 2 and 13 years, and 13 age-matched healthy subjects as controls. Circulating cytokine values were evaluated in basal conditions in all children, and 6 and 24 h following the 1st hGH injection (0.23 mg/kg per week), and then after 3 months of hGH treatment in GHD patients. Serum levels of IL-4, IL-6, IL-12 and TNF-alpha were measured by commercially available ELISAs. Results: No significant differences were found between controls and GHD children in basal values of serum IL-4, IL-6, IL-12 and TNF-alpha (P > 0.05 by Mann-Whitney U test). Analysis of cytokine levels during hGH treatment showed significant changes over time in TNF-alpha and IL-6 levels (P = 0.0014 and P = 0.00024 respectively), with the more pronounced effect observed at 6 h following the first administration of hGH (i.e. increase in IL-6 (Wilcoxon matched pairs test, P = 0.0015) and TNF-alpha levels (P = 0.0015)). No significant changes over time were observed in IL-4 and IL-12 serum levels. Conclusions: In vivo release of the pro-inflammatory cytokines IL-6 and TNF-alpha can be affected by hGH treatment in GHD children, suggesting a direct effect of GH on the immune function.