Human neonates are uniquely susceptible to group B streptococcal (GBS) infections. We have shown that neonatal mixed mononuclear cells have a deficiency in the production of the T helper-1 (Th-1) cytokine, interferon gamma (IFN-␥), and that incubation of neonatal neutrophils with recombinant IFN-␥ corrects these neutrophil defects. IL-12 and the more recently described IL-18 are also Th-1 type cytokines that are able to induce the production of IFN-␥ in the presence of bacteria and bacterial products. We examine the ability of GBS to induce the production of IFN-␥, IL-18, and IL-12 by cord blood mixed mononuclear cells and compared these results with the IFN-␥, IL-18, and IL-12 response of mixed mononuclear cells from adult blood. We demonstrate that cord blood mixed mononuclear cells produced significantly less IL-18 is a recently described member of the IL-1 cytokine family, which was initially defined as IFN-␥-inducing factor (1). IL-18 gene expression and/or protein secretion has been observed in macrophages (2), dendritic cells (3), mononuclear cells (4), keratinocytes (5), chondrocytes (6), pituitary and adrenal cells (7), astrocytes and microglia (8), and intestinal epithelial cells (9). Studies have elucidated a broad array of effector functions implicating IL-18 as an important regulator of both innate and acquired immune responses (10, 11). In animals, IL-18 contributes to protective immunity against a variety of pathogens, including Cryptococcus, Leishmania, Staphylococcus, Salmonella,.IL-12 is also an integral immune regulator, which promotes Th-1 responses while suppressing Th-2 responses (16,17). IL-12 is primarily produced by macrophages and dendritic cells and has been shown to induce the production of IFN-␥ by T cells and natural killer (NK) cells (18). Recent studies have focused on the interaction between IL-18 and IL-12 in certain inflammatory responses. In Th-1 immune responses, IL-18 and IL-12 are important cytokines that may synergistically stimulate IFN-␥ production and enhance NK and T cell-mediated cytotoxicity (19). Recent studies implicate the interaction of these Th-1 cytokines in the development of autoimmune diseases and suggest that regulating their function may be therapeutically beneficial (20,21).Early-onset GBS infections in neonates often lead to sepsis and severe septic shock, with an approximate 5-15% mortality rate (22)(23)(24)