EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR-1 ON NEUTROPHIL AND MONOCYTE FUNCTIONS IN NORMAL AND SEPTIC STATES

Background: Insulin-like growth factor 1 (IGF-1) mediates anabolic act ions in catabolic states and also influences the immune system. Endoge nous IGF-1 production is suppressed in sepsis; replacement therapy is therefore a natural approach to obtain the protein anabolic and potent ially immune-stimulating effects of IGF-1. Methods: Twenty-two piglets were randomized to three groups: an IGF-1 group (n = 8) receiving a c ontinuous infusion of 1.3 mg/h of IGF-1, a nontreated septic control g roup (n = 8), and a nonseptic control group (n = 6) receiving saline. Phagocytosis and respiratory burst in porcine neutrophils were evaluat ed by flow cytometry (FCM); tumor necrosis factor (TNF) levels were me asured in serum during the septic period. In addition, human neutrophi ls and monocytes were primed in vitro with IGF-1 and subsequently were stimulated with phorbol myristate acetate (PMA) or Escherichia coli; phagocytosis and respiratory burst were evaluated by FCM. Results: Und er nonseptic conditions, pretreatment with IGF-1 suppressed the abilit y of neutrophils to ingest bacteria (ie, the level of phagocytosis) 43 .4% +/- 2.7% (IGF-1-treated) vs 55.8% +/- 3.4% (nontreated septic cont rols) and 57.3% +/- 3.34% (nonseptic controls) (p = .01). When challen ged by live E. coli infusion, phagocytosis increased in the IGF-1 grou p to the levels of the nontreated group. The respiratory burst showed a convincing printing effect of IGF-1. After 4 hours of sepsis, the me an fluorescence intensity was 63.1 +/- 6.9 in the IGF-1 group and 40.7 +/- 3.0 in nontreated septic controls. The serum levels of TNF-alpha in the nontreated septic control group were twice those in the IGF-1-t reated group, ie, 65.7 +/- 13.1 pg/mL in the nontreated septic control s and 31.5 +/- 7.5 pg/mL, in the IGF-1 group (p = .03). In vitro primi ng of human neutrophils and monocytes with IGF-1 and subsequent stimul ation with PMA or E. coli demonstrated that IGF-1 enhanced both phagoc ytosis and respiratory burst. Conclusions: IGF-1 serves as a priming a gent for biologic functions of leukocytes.