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 actions in catabolic states and also influences the immune system. Endogenous IGF-1 production is suppressed in sepsis; replacement therapy is therefore a natural approach to obtain the protein anabolic and potentially immune-stimulating effects of IGF-1.


METHODS
Twenty-two piglets were randomized to three groups: an IGF-1 group (n = 8) receiving a continuous infusion of 1.3 mg/h of IGF-1, a nontreated septic control group (n = 8), and a nonseptic control group (n = 6) receiving saline. Phagocytosis and respiratory burst in porcine neutrophils were evaluated by flow cytometry (FCM); tumor necrosis factor (TNF) levels were measured in serum during the septic period. In addition, human neutrophils 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
Under nonseptic conditions, pretreatment with IGF-1 suppressed the ability of neutrophils to ingest bacteria (ie, the level of phagocytosis) 43.4% +/- 2.7% (IGF-1-treated) vs 55.8% +/- 3.4% (nontreated septic controls) and 57.3% +/- 3.34% (nonseptic controls) (p = .01). When challenged by live E. coli infusion, phagocytosis increased in the IGF-1 group to the levels of the nontreated group. The respiratory burst showed a convincing priming effect of IGF-1. After 4 hours of sepsis, the mean 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-treated group, ie, 65.7 +/- 13.1 pg/mL in the nontreated septic controls and 31.5 +/- 7.5 pg/mL in the IGF-1 group (p = .03). In vitro priming of human neutrophils and monocytes with IGF-1 and subsequent stimulation with PMA or E. coli demonstrated that IGF-1 enhanced both phagocytosis and respiratory burst.


CONCLUSIONS
IGF-1 serves as a priming agent for biologic functions of leukocytes.
Balteskard
L
L
Department of Surgery, Tromsø University Hospital, Norway.
Unneberg
K
K
Halvorsen
D
D
Hansen
J B
JB
Revhaug
A
A
D000818:Animals; D015925:Cryopreservation; D004926:Escherichia coli; D005434:Flow Cytometry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D010587:Phagocytosis; D016897:Respiratory Burst; D018805:Sepsis / Q000097:blood*; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007334:Insulin-Like Growth Factor I; D013755:Tetradecanoylphorbol Acetate