Abstract
The production of IL-10 by human neonatal blood mononuclear leukocytes(BML) stimulated with lipopolysaccharide (LPS), tumor necrosis factor-α(TNF-α), 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-α was ≈20 and ≈15%, respectively, of adult BML. The combination of human recombinant TNF-α 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-α could not be ruled out, because TNF-α production by LPS-stimulated newborn BML and the expression of TNF-α 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-α and its receptors.
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Abbreviations
- BML:
-
blood mononuclear leukocytes
- D-PBSE/CMF:
-
Dulbecco's PBS/calcium and magnesium-free
- LPS:
-
lipopolysaccharide
- NEC:
-
necrotizing enterocolitis
- PMA:
-
phorbol 12-myristate 13-acetate
- TNF-α:
-
tumor necrosis factor-α
- TNF-R:
-
tumor necrosis factor-α receptor
- NK:
-
natural killer
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Acknowledgements
Antibodies to human CD3 were kindly provided by Dr. Edward G. Brooks. The encouragement of Dr. Frank C. Schmalstieg, technical advice of Dr. Gang Ye, and the secretarial support of Susan C. Kovacevich and Freda Purnell are appreciated.
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Supported in part by grants from the Wyeth/Ayerst Nutritional Research and the Wyeth Pediatric Neonatology Research Fund.
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Chheda, S., Palkowetz, K., Garofalo, R. et al. Decreased Interleukin-10 Production by Neonatal Monocytes and T Cells: Relationship to Decreased Production and Expression of Tumor Necrosis Factor-α and Its Receptors. Pediatr Res 40, 475–483 (1996). https://doi.org/10.1203/00006450-199609000-00018
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DOI: https://doi.org/10.1203/00006450-199609000-00018
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