Increased neutrophil insulin-like growth factor-I (IGF-I) receptor expression and IGF-I-induced functional capacity...

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.