Decreased interleukin-10 production by neonatal monocytes and T cells: relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors.
The production of IL-10 by human neonatal blood mononuclear leukocytes (BML) stimulated with lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), antibodies to CD3, or phorbol 12-myristate 13-acetate (PMA) was measured. The production of IL-10 by neonatal BML cultured with LPS or TNF-alpha was approximately 20 and approximately 15%, respectively, of adult BML. The combination of human recombinant TNF-alpha and LPS failed to augment IL-10 production in neonatal BML. The decreased production of IL-10 by neonatal leukocytes was not due to an autocrine feedback mechanism because only low concentrations of IL-10 were found in newborn sera. A connection with TNF-alpha could not be ruled out, because TNF-alpha production by LPS-stimulated newborn BML and the expression of TNF-alpha receptors on newborn monocytes were reduced. Mean +/- SD of concentrations of IL-10 in supernatants from adult and neonatal BML after stimulation with antibodies to human CD3 for 48 or 72 h were 914 +/- 386 and 178 +/- 176 pg/mL, respectively (p < 0.0001). In experiments with enriched populations of neonatal T cells, the addition of PMA failed to augment IL-10 production. This suggested that newborn T cells may be in a different state of activation than adult T cells Thus, IL-10 production in neonatal monocytes and T cells is reduced and this study suggests that the reduction may be secondary in part to regulatory processes involving TNF-alpha and its receptors.
Chheda
S
S
University of Texas Medical Branch, Department of Pediatrics, Galveston 77555-0369, USA.
Palkowetz
K H
KH
Garofalo
R
R
Rassin
D K
DK
Goldman
A S
AS
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D016753:Interleukin-10 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D016014:Linear Models; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D012016:Reference Values; D013268:Stimulation, Chemical; D013601:T-Lymphocytes / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D008070:Lipopolysaccharides; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10