title: Skewed pattern of Toll-like receptor 4-mediated cytokine production in human neonatal blood: low LPS-induced IL-12p70 and high IL-10 persist throughout the first month of life.
abstract: Newborns are highly susceptible to infectious diseases, which may be due to impaired immune responses. This study aims to characterize the ontogeny of neonatal TLR-based innate immunity during the first month of life. Cellularity and Toll-like receptor (TLR) agonist-induced cytokine production were compared between cord blood obtained from healthy neonates born after uncomplicated gestation and delivery (n=18), neonatal venous blood obtained at the age of one month (n=96), and adult venous blood (n=17). Cord blood TLR agonist-induced production of the Th1-polarizing cytokines IL-12p70 and IFN-alpha was generally impaired, but for TLR3, 7 and 9 agonists, rapidly increased to adult levels during the first month of life. In contrast, TLR4 demonstrated a slower maturation, with low LPS-induced IL-12p70 production and high IL-10 production up until the age of one month. Polarization in neonatal cytokine responses to LPS could contribute to neonatal susceptibility to severe bacterial infection.
authors: Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors: M E
authors: ME
authors: Belderbos
authors: G M
authors: GM
authors: van Bleek
authors: O
authors: O
authors: Levy
authors: M O
authors: MO
authors: Blanken
authors: M L
authors: ML
authors: Houben
authors: L
authors: L
authors: Schuijff
authors: J L L
authors: JL
authors: Kimpen
authors: L
authors: L
authors: Bont
mesh_terms: D000328:Adult; D001769:Blood / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000097:blood*; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000254:growth & development* / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007231:Infant, Newborn; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000097:blood* / Q000378:metabolism; D053765:Interleukin-12 Subunit p35 / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010949:Plasma / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D051193:Toll-Like Receptors / Q000819:agonists; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; C508858:IL12A protein, human; C500879:IL12B protein, human; D016898:Interferon-alpha; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma