INCREASED NEUTROPHIL INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) RECEPTOR EXPRESSION AND IGF-I-INDUCED FUNCTIONAL-CAPACITY IN PATIENTS WITH UNTREATED LARON SYNDROME

Insulin-like growth factor-I (IGF-I) is a growth hormone-dependent pep tide with growth and immunoregulatory properties, and in Laron syndrom e growth hormone insensitivity induces impaired production of IGF-I, I n the present study we have determined the neutrophil expression of IG F-I receptors (IGF-I-Rs), as well as the IGF-I-induced priming of neut rophil functional capacity, in two children with Laron syndrome treate d with recombinant human IGF-I, and in age-matched controls, Before tr eatment, the patient neutrophil expression of IGF-I-Rs was significant ly increased, However, with replacement therapy the neutrophil IGF-I-R expression was downregulated to levels similar to those of the contro ls within one month, In the patients, the phagocytic capacity and oxid ative burst of unprimed neutrophils were normal and similar to control s before the start of treatment. Moreover, IGF-I efficiently primed bo th patient and control neutrophils to increase their phagocytic capaci ty 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 studi es 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 .