Neonates are uniquely susceptible to group B streptococcal (GBS) infections. Defective neonatal polymorphonuclear leukocyte (PMN) movement and respiratory burst contribute to this susceptibility to infection. We have shown that neonatal mixed mononuclear cells (MMCs) are deficient in their production of the T-helper-1 (Th-1)cytokine interferon gamma (IFN-γ) and incubation of neonatal PMNs with recombinant IFN-γ corrects these defects. Interleukin-12 (IL-12) and interleukin-18 (IL-18) are Th-1 cytokines that induce IFN-γ production. We have demonstrated that cord blood MMCs produce significantly less IFN-γ, IL-12, and IL-18 in response to GBS, and that the cord blood MMC production of IFN-γ is enhanced by recombinant IL-12 and IL-18 (Ped. Res.54:276-281, 2003). Recently, we have shown that IL-18 can enhance the motility of neonatal PMN's. Here we examine the role of IL-12 and IL-18 on PMN respiratory burst. Cord blood PMNs have significantly less respiratory burst activation measured by phorbol-myristate-acetate stimulated dihydrorhodamine fluorescence than PMNs obtained from adults [mean/sem: cord (87/7) adult (115/7) p≤.01]. The incubation of cord blood PMNs with IL-18 (100 ng/ml 0.1 ng/ml) enhanced the respiratory burst activation equal to the activity produced by the similarly treated PMNs from adults [mean/sem: 100ng/ml cord (118/10), adult (123/11); 10 ng/ml cord (125/14), adult (126/4); 1 ng/ml cord (117/9), adult (114/5); 0.10 ng/ml cord (111/7), adult (122/20)] and equal to the untreated adult control. The IL-18 treated cord blood PMNs demonstrated significantly greater respiratory burst activity than the untreated control cord PMNs (p≤.05). The incubation of cord blood PMNs with IL-12 (100 ng/ml-0.1 ng/ml) did not influence respiratory burst. The respiratory burst activity of cord blood PMNs treated with IL-12 remained lower than similarly treated PMNs from adults [(mean/sem): 100 ng/ml cord (93/11), adult (122/24); 10 ng/ml cord (87/8), adult (127/25); 1 ng/ml cord (86/4), adult (117/16); 0.1ng/ml cord (87/9), adult (119/4) (p≤.01 all concentrations)] and equal to the untreated cord blood PMNs. These data and our cumulative experience suggest that the deficiency of the Th-1 cytokines IL-12 and IL-18 by neonates can contribute to defective IFN-γ production. While IL-12 alone appears to have no effect on neonatal PMN respiratory burst, IL-18 can significantly enhance both respiratory burst activation and movement. The combined deficiencies in the production of the Th-1 cytokines IFN-γ, IL-12, and IL-18 likely contributes to the neonates enhanced susceptibility to GBS and other infections.
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