Abstract 1546 Neonatal Immunology & Hematology Poster Symposium, Monday, 5/3

Group B streptococci (GBS) are a major cause of infection in neonates and other immunocompromised hosts. Defective phagocyte function and antibody deficiency are major risk factors for developing GBS infection. Wilson and colleagues (J Clin Invest 77:860, 1986) have reported that neonates have a deficiency in production of the major phagocyte activator interferon-gamma (IFN-gamma), and we have shown that recombinant human IFN-gamma enhances activation and movement of polymorphonuclear leukocytes (PMNs) from newborns (J Exp Med 173:767, 1991). Interleukin 12 (IL-12) is a Th1 type cytokine which enhances the production of IFN-gamma. In the present study, we examined transcription and translation of IL-12 and IFN-gamma by mononuclear cells (MNCs) from cord bloods and adults in response to GBS. Comparative reverse transcriptase (RT) PCR was utilized to assess IL-12 and IFN-gamma mRNA production with the constitutively expressed glyceraldehyde 3 phosphate dehydrogenase (G3PDH) gene serving as the internal control. Translation of mRNA into IL-12 and IFN-gamma protein was determined by quantitative ELISA. After 18 hours of incubation with GBS, cord blood MNCs made significantly less IFN-gamma (p<0.005) than did MNCs from adults. We also found that IL-12, which stimulates the production of IFN-gamma, was produced in lower amounts of GBS exposed cord blood MNCs compared to those from adults (p<0.003). We next examined transcription of IL-12 and IFN-gamma by RT-PCR and found that cord MNCs transcribed less mRNA for both of these critical cytokines than did MNCs from adults (IFN-gamma, p<0.009; IL-12, p<0.021). These data indicate that cord blood MNCs have a deficiency in the ability to transcribe and translate mRNA for these two essential cytokines in host defense. This likely contributes to the unique susceptibility of neonates to GBS infections.