TNF-alpha 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 0.03-0.04mg/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-alpha0), and at 6 (TNF-alpha6) and 12 (TNF-alpha12) months of the treatment with rhGH. TNF-alpha was determined using a human TNF-alpha ELISA assay (Biosource International).

Results: TNF-alpha0 levels were significantly higher in children with GHD than in controls (41.79+/-25.04 and 8.63+/-4.48pg/ml, respectively, p<0.001) and decreased significantly during rhGH treatment (TNF-alpha0=41.79+/-25.04, TNF-alpha6=13.67+/-9.95, TNF-alpha12=10.86+/-6.61pg/ml, p<0.05). There was no correlation between TNF-alpha levels and BMI, IGF-1/logIGF1, 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.