Insulin-like growth factor-I (
IGF-I) is a
growth hormone-dependent
peptide with growth and immunoregulatory properties, and in
Laron syndrome growth hormone insensitivity induces impaired production of
IGF-I. In the present study we have determined the neutrophil expression of
IGF-I receptors (
IGF-I-Rs), as well as the
IGF-I-induced priming of neutrophil functional capacity, in two children with
Laron syndrome treated with recombinant human
IGF-I, and in age-matched controls. Before treatment, the patient neutrophil expression of
IGF-I-Rs was significantly increased. However, with replacement
therapy the neutrophil
IGF-I-R expression was downregulated to levels similar to those of the controls within one month. In the patients, the phagocytic capacity and oxidative burst of unprimed neutrophils were normal and similar to controls before the start of treatment. Moreover,
IGF-I efficiently primed both patient and control neutrophils to increase their phagocytic capacity and oxidative burst in vitro. However, before
therapy, the priming response to
IGF-I was significantly stronger in the neutrophils in the patients than in the controls. The present data support earlier studies by us and others demonstrating that
IGF-I is a potent regulator of mature neutrophil function, but also suggest that these leukocytes may function normally in the presence of very low levels of
IGF-I in vivo.