In-vitro response of erythroid progenitors from children with thalassaemia major to human growth hormone and insulin-like growth factor I.

Objective: Most short-statured children with beta-thalassaemia major have markedly reduced levels of circulating insulin-like growth factor I (IGF-I). Both human growth hormone (hGH) and IGF-I enhance the in-vitro growth of erythroid progenitors, with hGH exerting its effects via paracrine production of IGF-I. The aim of this study was to characterize further the hGH-IGF-I axis abnormalities in thalassaemia major by evaluating the erythroid potentiating effects of both peptides in cultures of thalassaemic and control erythroid progenitors.

Design: Ten short-statured thalassaemic children and nine age-matched healthy donors were evaluated for the in-vitro response of their peripheral blood erythroid progenitors to stimulation with hGH and IGF-I.

Measurements: The frequency of erythroid progenitors in serum-free cultures of thalassaemic and control peripheral blood mononuclear cells was enumerated following 14 days of incubation in the presence of hGH or IGF-I.

Results: Biosynthetic hGH induced a similar dose-dependent magnitude of colony enhancement in cultures of erythroid progenitors from thalassaemic children, as compared to controls. Significant enhancement of colony growth was detected at 42 mU/l hGH, with a maximal effect detected at 83 mU/l of this hormone (173 +/- 8 vs 153 +/- 9% of baseline erythroid progenitors in patients versus controls, respectively). Enhancement of both thalassaemic and control erythroid precursors by hGH was completely abrogated by monoclonal antibodies (alpha IR-3) directed against the IGF-I membrane receptor, thereby confirming the normal capacity of thalassaemic accessory cells to produce IGF-I in response to hGH. Biosynthetic IGF-I also enhanced the growth of thalassaemic and control erythroid precursors to 172 +/- 17 and 159 +/- 10% of baseline at 100 and 10 U/l, respectively.

Conclusions: Our detection of a normal capacity of thalassaemic peripheral blood target cells to response to hGH and IGF-I suggests that these patients do not suffer from a specific defect in receptor and/or post-receptor mechanism(s) involving the response of these cells to both peptides. The normal responsiveness of thalassaemic target cells to hGH and IGF-I suggests that both peptides may be useful in the treatment of growth retardation in thalassaemia.