Insulin-like growth factor-I regulates the neonatal immune response in infection and maturation by suppression of IFN-γ.
Disturbances in Insulin-like growth factor-I (IGF-I) and dysregulation in neonatal immune responses have been associated with typical neonatal diseases. Immunosuppression by IGF-I might be a key regulator of neonatal immune responses in infection and maturation. However, information on IGF-I serum levels, IGF-I-receptor (IGF-IR) and effects on functional properties of neonatal immune cells is scarce. Neonatal cord blood samples were stimulated with anti-CD3/anti-CD28, PMA/ionomycin or LPS in a whole-blood assay, while IGF-I serum levels and IGF-I receptor expression were assessed. Furthermore the effect of IGF-I on cytokine expression, apoptosis and the DNA binding activity of AP-1 and NFκB was evaluated. IGF-I serum levels were within normal range. The IGF-I-receptor was present on the surface of cord blood CD3+CD4+lymphocytes and cord blood CD14+monocytes. Upon stimulation the IGF-I-R expression on lymphocytes was significantly upregulated. The addition of IGF-I (100ng/ml) to whole blood cultures inhibited the secretion of IFN-γ from PMA/ionomycin-stimulated cord blood mononuclear cells (CBMC). While IGF-I did not influence apoptosis in our experimental setting, it led to a distinct decrease in anti-CD3/CD28-stimulated DNA binding activity of AP-1 and NFκB. Thus IGF-I may be a key regulator of neonatal immune responses in maturation processes and inflammation by suppressing proinflammatory Th1 responses. Future in vivo studies need to elucidate whether disturbances of the IGF-I serum level and IGF-IR expression are associated with susceptibility for infections and subsequent diseases in neonates.
Department of Pediatrics, Albert-Ludwigs-University of Freiburg, Mathildenstrasse 1, D-79106 Freiburg, Germany. alexander.puzik@uniklinik-freiburg.de
Alexander
A
Puzik
Jan
J
Rupp
Birte
B
Tröger
Wolfgang
W
Göpel
Egbert
E
Herting
Christoph
C
Härtel
D017209:Apoptosis / Q000276:immunology; D018106:CD28 Antigens / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology*; D007231:Infant, Newborn; D007239:Infections / Q000097:blood / Q000276:immunology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D017526:Receptor, IGF Type 1 / Q000097:blood; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018106:CD28 Antigens; D017252:CD3 Complex; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma; D004247:DNA; D017526:Receptor, IGF Type 1