Effects of group B streptococci on cord and adult mononuclear cell interleukin-12 and interferon-gamma mRNA accumulation and protein secretion.

Group B streptococci (GBS) are a major cause of early-onset infection in neonates. Neonates, who have defects in neutrophil function that likely contribute to susceptibility to GBS infection, are deficient in the production of the phagocyte activator interferon (IFN)-gamma. GBS-stimulated mRNA accumulation and protein secretion of IFN-gamma and interleukin (IL)-12, a major enhancer of IFN-gamma production, by mixed mononuclear cells (MMCs) from umbilical cord and adult peripheral blood was examined. GBS-exposed cord blood MMCs secreted lower concentrations of both IL-12 and IFN-gamma proteins than did MMCs from adults. IL-12 and IFN-gamma mRNA accumulation was examined by use of comparative reverse transcriptase-polymerase chain reaction. Cord blood MMCs accumulated less mRNA for both IL-12 and IFN-gamma than did adult blood MMC. The deficiency in cord blood cell production of IL-12 may have a role in inadequate IFN-gamma production, which contributes to the unique susceptibility of neonates to GBS infections.

Outcome of infants weighing less than 800 grams at birth: 15 years' experience.

OBJECTIVE: Mortality and neurodevelopmental morbidity among infants weighing less than 800 g at birth are compared in three separate studies from the same intensive care nursery during an almost 15-year period. METHODS: The survival and neurodevelopmental outcome of 210 infants with birth weights less than 800 g admitted to the University of Washington neonatal intensive care unit between 1986 and 1990 are compared with those of two previous cohorts (1977 through 1980 and 1983 through 1985) of extremely low birth weight (ELBW) infants from the same nursery. RESULTS: Annual admissions of these ELBW infants nearly doubled from 1977 to 1990, whereas nursery survival rose from 20% between 1977 and 1980, to 36% between 1983 and 1985, to 49% in this current study of births between 1986 and 1990. The greatest increase in survival among the three studies occurred among infants with birth weights less than 700 g. Female survival was 20% higher than male survival in each of the time periods. The prevalence of major neurosensory impairments did not differ significantly among the three study groups (19%, 21%, and 22% respectively); male survivors were more commonly affected across time periods. There were no differences in mean cognitive test scores between the current 1986 through 1990 birth cohort (94) and the two previous cohorts (1977 through 1980, 98; 1983 through 1985, 89). CONCLUSIONS: The experience of our center with these ELBW infants over time seems reassuring to the extent that progressive increases in nursery survival have not resulted in increased neurodevelopmental morbidity.

P-selectin regulates platelet-activating factor synthesis and phagocytosis by monocytes.

Adhesion molecules on endothelial cells or platelets may regulate localization and activation of leukocytes at sites of tissue injury, infection, or thrombosis. In these studies, we found that human peripheral blood monocytes adhered specifically to immobilized P-selectin (CD62P), Chinese hamster ovary cells transfected with a cDNA for P-selectin, or endothelial cells stimulated to express P-selectin on the cell surface. P-selectin did not directly stimulate synthesis of the lipid autoacoid platelet-activating factor (PAF); however, incubation on immobilized P-selectin primed monocytes for increased synthesis of PAF in response to opsonized zymosan particles. P-selectin did not stimulate increased surface expression of integrin CD11b/CD18 and did not enhance binding of iC3b-coated erythrocytes, a CD11b/CD18-mediated functional response. P-selectin increased PAF production by monocytes incubated with unopsonized zymosan particles that stimulate this response by interaction with the beta-glucan receptor. Further, phagocytosis of unopsonized zymosan particles, another response triggered by the beta-glucan receptor, was increased following the adherence of monocytes to P-selectin. These data suggested that P-selectin primed monocytes for increased PAF synthesis through regulation of the beta-glucan receptor or regulation of signal transduction mechanisms that are linked to the receptor. P-selectin expressed on endothelial cells or platelets may serve both to localize monocytes at sites of vascular inflammation or thrombosis and to prime the cells for subsequent responses that augment inflammation.

Immunomodifiers applicable to the prevention and management of infectious diseases in children.

Attempts to augment immune function in infants or children with overwhelming sepsis or immune deficiency have focused on recombinant cytokines and interferons. Although early in their clinical use, the proinflammatory and antiinflammatory effects of the interleukins show promise in regulating the acute inflammatory response. The hematopoietic growth factors have demonstrated considerable clinical effect, especially in individuals with distinct hematopoietic disorders and in patients receiving immunosuppressive chemotherapy. The interferons gamma and alpha have received considerable attention over the last decade as potential immunomodulators. The stimulatory effects of INF-gamma on human neutrophils suggest its therapeutic usefulness in children with specific neutrophil dysfunction, and INF-alpha has shown broad clinical application both as an antitumor as well as an antiviral agent. The most recent studies of the integrins and selectins implicate their potential role in regulating a number of infectious disease states. As we learn more about the complexity of interactions and the delicate balance these molecules have in regulating the immune response, we will be better able to implement their use in regulating disease states in infants and children.