Defective production of IL-18 and IL-12 by cord blood mononuclear cells influences the T helper-1 interferon gamma response to group B streptococci

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-gamma), and that incubation of neonatal neutrophils with recombinant IFN-gamma 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-gamma in the presence of bacteria and bacterial products. We examine the ability of GBS to induce the production of IFN-gamma, IL-18, and IL-12 by cord blood mixed mononuclear cells and compared these results with the IFN-gamma, IL-18, and IL-12 response of mixed mononuclear cells from adult blood. We demonstrate that cord blood mixed mononuclear cells produced significantly less IFN-gamma, IL-18, and IL-12 in response to GBS compared with mixed mononuclear cells from adults. Cord blood mixed mononuclear cells' production of IFN-gamma is enhanced by added recombinant IL-18 and IL-12. The maximal cord blood cell production of IFN-gamma, in response to GB S, is achieved by priming the cells with both IL-18 and IL-12. We conclude that neonatal mixed mononuclear cells exhibit deficiencies in three main Th-1 type cytokine responses, IFN-gamma, IL-12, and IL-18. This combined Th-1 type cytokine deficiency may contribute to the enhanced susceptibility of the human neonate to GBS and other microbial infections.