HIGH-LEVEL INTERLEUKIN-12 PRODUCTION, BUT DIMINISHED INTERFERON-GAMMAPRODUCTION, BY CORD-BLOOD MONONUCLEAR-CELLS

Cell-mediated immunity (CMI) in neonates is relatively de deficient wh en compared with adults. Defects in cytokine production and/or regulat ion may contribute to heightened susceptibility to infection by intrac ellular pathogens. The heterodimeric cytokine IL-12 is a key regulator of CMI and inducer of interferon-gamma (IFN-gamma) production. We rep ort here that umbilical cord blood-derived mononuclear cells (MNC) are capable of producing IL-12 (p40 subunit, measured by RIA, and IL-12 p 70 heterodimer, by ELISA) at levels comparable to or greater than adul t peripheral blood MNC, after stimulation with heat-killed Staphylococ cus aureus in 18-h cultures. As in adult MNC, S. aureus induced IL-12 p40 mRNA accumulation in cord blood MNC. IFN-gamma was also produced i n the S. aureus-stimulated cultures, in an IL-12-dependent manner, but cord blood MNC produced 5-fold lower levels of IFN-gamma compared wit h adult MNC (p < 0.05). Preincubation with IL-10 inhibited IL-12 p40 p roduction by cord blood and adult peripheral blood MNC in a dose-depen dent fashion, whereas neutralization of endogenous IL-10 enhanced IL-1 2 and IFN-gamma levels. The results demonstrate that the relative CMI deficiency in neonates is not due to an intrinsic defect in the capaci ty of neonatal MNC to produce IL-12. The underlying factors responsibl e for diminished IFN-gamma production are not known, but may lie in th e balance of stimulatory and inhibitory signals delivered to the IFN-g amma secreting cells along with IL-12, or may relate more to the absen ce of memory T cells among cord blood MNC.