The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn

Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord bl...

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Bibliographic Details
Published in:Journal of Immunology 2006-08, Vol.177 (3), p.1956-1966
Main Authors: Levy, Ofer, Coughlin, Melissa, Cronstein, Bruce N, Roy, Rene M, Desai, Avani, Wessels, Michael R
Format: Article
Language:English
Subjects:
Adenosine - pharmacology
Adenosine A3 Receptor Antagonists
Adenosine Deaminase - physiology
Adult
Bacterial Proteins - antagonists & inhibitors
Bacterial Proteins - blood
Bacterial Proteins - pharmacology
Cyclic AMP - biosynthesis
Cyclic AMP - blood
Cyclic AMP - physiology
Escherichia coli
Fetal Blood - cytology
Fetal Blood - immunology
Fetal Blood - metabolism
Humans
Immunologic Factors - antagonists & inhibitors
Immunologic Factors - blood
Immunologic Factors - physiology
Infant, Newborn
Interleukin-6 - biosynthesis
Leukocytes, Mononuclear - enzymology
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Lipopeptides
Lipoproteins - antagonists & inhibitors
Lipoproteins - blood
Lipoproteins - pharmacology
Listeria monocytogenes
Macrophage Activation - immunology
Oligopeptides - pharmacology
Receptor, Adenosine A3 - blood
Receptor, Adenosine A3 - physiology
Signal Transduction - immunology
Toll-Like Receptors - antagonists & inhibitors
Toll-Like Receptors - blood
Toll-Like Receptors - physiology
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - biosynthesis
Up-Regulation - immunology
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Summary:Human newborns are susceptible to microbial infection and mount poor vaccine responses, yet the mechanisms underlying their susceptibility are incompletely defined. We have previously reported that despite normal basal expression of TLRs and associated signaling intermediates, human neonatal cord blood monocytes demonstrate severe impairment in TNF-alpha production in response to triacylated (TLR 2/1) and diacylated (TLR 2/6) bacterial lipopeptides (BLPs). We now demonstrate that in marked contrast, BLP-induced synthesis of IL-6, a cytokine with anti-inflammatory and Th2-polarizing properties, is actually greater in neonates than adults. Remarkably, newborn blood plasma confers substantially reduced BLP-induced monocyte synthesis of TNF-alpha, while preserving IL-6 synthesis, reflecting the presence in neonatal blood plasma of a soluble, low molecular mass inhibitory factor (
ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.177.3.1956