TNF-α levels in children with growth hormone deficiency and the effect of long-term growth hormone replacement therapy

ObjectiveGrowth hormone (GH) has been suggested to modulate the release of some cytokines including TNF-α.To investigate TNF-α levels in children with GH deficiency (GHD), to evaluate alteration in TNF-α levels during recombinant human GH (rhGH) treatment, and to analyze possible correlations between TNF-α and GH, IGF-1 and IGFBP-3.DesignTwenty-four children, aged 12.60 ± 2.27 years, with isolated GHD and given rhGH therapy, as subcutaneous ingestion of 0.03–0.04 mg/kg once-daily dose, were evaluated. Eleven had complete and 13 had partial GHD. Thirty-three healthy children were studied as controls. Age and sex distribution, body mass indexes of two groups were similar. In children with GHD, blood samples were drawn before (TNF-α0), and at 6 (TNF-α6) and 12 (TNF-α12) months of the treatment with rhGH. TNF-α was determined using a human TNF-α ELISA assay (Biosource International).ResultsTNF-α0 levels were significantly higher in children with GHD than in controls (41.79 ± 25.04 and 8.63 ± 4.48 pg/ml, respectively, p < 0.001) and decreased significantly during rhGH treatment (TNF-α0 = 41.79 ± 25.04, TNF-α6 = 13.67 ± 9.95, TNF-α12 = 10.86 ± 6.61 pg/ml, p < 0.05).There was no correlation between TNF-α levels and BMI, IGF-1/log IGF1, IGFBP-3 levels and growth velocity of the patients with GHD.Although no correlation between TNF-α and peak GH levels after stimulation was present; a moderate reverse correlation between TNF-α and basal serum concentrations of GH (r = −0.512, p = 0.046) was demonstrated.ConclusionsTNF-α levels are significantly higher in children with GHD than the controls, and long-term therapy with rhGH effectively reduces its level. Our data suggest that GH plays an inhibitory role on TNF-α release in humans. However, due to inconsistent results up to now, further prospective, controlled and long term studies are needed to elucidate the issue.