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

Objective: Growth hormone (GH) has been suggested to modulate the release of some cytokines including TNF-alpha. To investigate TNF-alpha levels in children with GH deficiency (GHD), to evaluate alteration in TNF-alpha levels during recombinant human GH (rhGH) treatment, and to analyze possible correlations between TNF-alpha and GH, IGF-1 and IGFBP-3. Design: Twenty-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-alpha 0), and at 6 (TNF-alpha 6) and 12 (TNF-alpha 12) months of the treatment with rhGH. TNF-alpha was determined using a human TNF-alpha ELISA assay (Biosource International). Results: TNF-alpha 0 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-alpha 0=41.79 +/- 25.04, TNF-alpha 6=13.67 +/- 9.95, TNF-alpha 12=10.86 +/- 6.61 pg/ml, p<0.05). There was no correlation between TNF-alpha levels and BMI, IGF-1/logIGF2, IGFBP-3 levels and growth velocity of the patients with GHD. Although no correlation between TNF-alpha and peak GH levels after stimulation was present; a moderate reverse correlation between TNF-alpha and basal serum concentrations of GH (r=-0.512, p=0.046) was demonstrated. Conclusions: TNF-alpha 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-alpha release in humans. However, due to inconsistent results up to now, further prospective, controlled and long term studies are needed to elucidate the issue. (C) 2007 Elsevier Ltd. All rights reserved.