Decreased interleukin-10 production by neonatal monocytes and T cells: Relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors

Decreased interleukin-10 production by neonatal monocytes and T cells: Relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors
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DOI:
10.1203/00006450-199609000-00018
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发表时间:
1996-09-01
期刊:
影响因子:
3.6
通讯作者:
Goldman, AS
Goldman, AS
中科院分区:
医学3区
文献类型:
--
作者:
Chheda, S;Palkowetz, KH;Goldman, AS

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用脂多糖(LPS)、肿瘤坏死因子- α (tnf - α)、CD3抗体或phorbol 12-肉豆蔻酸13-醋酸酯(PMA)刺激新生儿血单核白细胞(BML)产生IL-10。用LPS或tnf - α培养的新生BML产生的IL-10分别相当于成年BML的20%和15%。人重组tnf - α和LPS联合使用不能增加新生儿BML中IL-10的产生。新生儿白细胞产生IL-10的减少不是由于自分泌反馈机制,因为在新生儿血清中只发现低浓度的IL-10。不能排除与tnf - α的联系,因为lps刺激新生儿BML产生tnf - α和新生儿单核细胞上tnf - α受体的表达减少。人CD3抗体刺激48 h和72 h后,成人和新生儿BML上清液中IL-10的平均+/- SD分别为914 +/- 386和178 +/- 176 pg/mL (p < 0.0001)。在富集新生T细胞群体的实验中,PMA的加入未能增加IL-10的产生。这表明新生儿T细胞可能处于与成人T细胞不同的激活状态,因此,新生儿单核细胞和T细胞中IL-10的产生减少,本研究表明,这种减少可能部分继发于涉及tnf - α及其受体的调节过程。
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 similar to 20 and similar to 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). Ln 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.