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-acet ate (PMA) was measured. The production of IL-10 by neonatal BML cultur ed with LPS or TNF-alpha was similar to 20 and similar to 15%, respect ively, of adult BML. The combination of human recombinant TNF-alpha an d LPS failed to augment IL-10 production in neonatal BML. The decrease d production of IL-10 by neonatal leukocytes was not due to an autocri ne feedback mechanism because only low concentrations of IL-10 were fo und in newborn sera. A connection with TNF-alpha could not be ruled ou t, because TNF-alpha production by LPS-stimulated newborn BML and the expression of TNF-alpha receptors on newborn monocytes were reduced. M ean +/- SD of concentrations of IL-10 in supernatants from adult and n eonatal BML after stimulation with antibodies to human CD3 for 48 or 7 2 h were 914 +/- 386 and 178 +/- 176 pg/mL, respectively (p < 0.0001). Ln experiments with enriched populations of neonatal T cells, the add ition of PMA failed to augment IL-10 production. This suggested that n ewborn 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 redu ced and this study suggests that the reduction may be secondary in par t to regulatory processes involving TNF-alpha and its receptors.