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Journal of Parenteral and Enteral Nutrition
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Effects of Insulin-Like Growth Factor 1 on Neutrophil and Monocyte Functions in Normal and Septic States

Lise Balteskard, MD, PHD

Department of Surgery, Tromsø University Hospital, Tromsø, Norway

Kjetil Unneberg, MD, PHD

Department of Surgery, Tromsø University Hospital, Tromsø, Norway

Dag Halvorsen, MD

Department of Internal Medicine, Tromsø University Hospital, Tromsø, Norway

John-Bjarne Hansen, MD, PHD

Department of Internal Medicine, Tromsø University Hospital, Tromsø, Norway

Arthur Revhaug, MD, PHD

Department of Surgery, Tromsø University Hospital, Tromsø, Norway

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. (Journal of Parenteral and Enteral Nutrition 22:127-135, 1998)

Journal of Parenteral and Enteral Nutrition, Vol. 22, No. 3, 127-135 (1998)
DOI: 10.1177/0148607198022003127


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