Stimulating effect of growth hormone on cytokine release in children

Objective: The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their relation with IGF-I levels in normal short stature children. Design and methods: 23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean+/-S.D. chronological age was 11.95+/-1.85 years (from 8.80 to 14.89 years), and mean+/-S.D. bone age was 10.48+/-2.44 years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex- and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children. and 12 h following the 4th GH subcutaneous injection in the 23 short children only. Results: No significant differences were found between short children and controls in basal values of serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to 338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; P < 0.00001). No significant differences were found between short children and controls in basal concentrations of serum INF-gamma (19+/-4 and 26+/-5 mIU/ml respectively), IL-1alpha (24.950+/-3.613 and 20.896+/-2.778 pg/ml respectively). IL-2 (3.945+/-1.209 and 4.794+/-0.562 pg/ml respectively). IL-12 (1.093+/-0.269 and 1.976+/-0.596 pg/ml respectively), and TNF-alpha (1.794+/-0.559 and 2.188+/-0.346 pg/ml respectively). Likewise. a significant increase was found in serum INF-gamma (before 19+/-4 and after four GH injections 185+/-57 mIU/ml respectively; P < 0.008), IL-1beta (24.950+/-3.613 to 43.339+/-5.431 pg/ml respectively; P < 0.0001), IL-2 (3.945+/-1.209 to 9.165+/-2.331 pg/ml respectively; P < 0.003). IL-12 (1.093+/-0.269 to 3.724+/-0.637 pg/ml respectively: P < 0.0007) and TNF-alpha (1.794+/-0.559 to 9.266+/-3.066 pg/ml respectively; P < 0.01). Conclusions: Cytokine release can be affected by short-term GH administration in normal children indicating a direct influence of GH on the immune system.