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 GBS, 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.
Department of Pathology, University of Utah School of Medicine, 50 North Medical Rm. 5B114, Salt Lake City, UT 84132, U.S.A.
Timothy R
TR
La Pine
Joanna L
JL
Joyner
Nancy H
NH
Augustine
Spencer D
SD
Kwak
Harry R
HR
Hill
D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D013290:Streptococcal Infections / Q000276:immunology*; D013292:Streptococcus agalactiae / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
D000911:Antibodies, Monoclonal; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma