Enhanced survival during experimental Listeria monocytogenes sepsis in neonatal mice prophylactically treated with Th1 and macrophage immunoregulatory cytokines and mediators.

BACKGROUND: Impairments in T-cell and macrophage-mediated host defense lead to increased infection-related morbidity and mortality in neonates, partly because of immaturity in T helper (Th)1 function. Listeria monocytogenes (Lm) is an intracellular pathogen disproportionately causing severe disease among neonates and the immunocompromised. Intact macrophage and Th1-mediated immune responses are critical for Lm clearance. We and others have previously demonstrated downregulation of Th1 and macrophage immunoregulatory cytokines in cord blood versus adult peripheral blood. We sought to determine whether therapeutic or prophylactic single agent or combination recombinant murine interleukin (rmIL)-12, rmIL-18, recombinant murine macrophage-colony stimulating factor (rmM-CSF), recombinant murine granulocyte macrophage-colony stimulating factor (rmGM-CSF) and recombinant murine interferon (rmIFN)-γ would enhance survival during experimental neonatal Lm sepsis. METHODS: A 90% lethal dose (LD90) of Lm was established in C57/BL/6 neonatal mice. rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and rmIFN-γ were administered singly or sequentially, before or after LD90 Lm inoculation; ampicillin was administered 24 hours after inoculation. RESULTS: Therapeutic doses of rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and rmIFN-γ as single agents and sequential therapy with rmM-CSF + (rmIL-12 and/or rmIL-18) + rmIFN-γ in addition to ampicillin were not associated with increased survival. However, prophylactic single doses of rmIL-12, rmIL-18, rmM-CSF and rmIFN-γ and prophylactic sequential doses of rmM-CSF + (rmIL-12 and/or rmIL-18) + rmIFN-γ in addition to ampicillin were associated with significantly enhanced survival compared with ampicillin alone. CONCLUSIONS: These data suggest prophylactic administration of macrophage and Th1 immunoregulatory cytokines can potentially overcome deficits in neonatal immunity to protect against Lm.

Is the new definition of bronchopulmonary dysplasia more useful?

OBJECTIVE: To determine the incidence of bronchopulmonary dysplasia (BPD) in low birth weight (LBW) infants <1251 g managed with early bubble nasal continuous positive airway pressure (NCPAP) and a gentle ventilation strategy using the newly proposed definition for BPD and the previous definitions. METHODS: Needs for supplemental oxygen and positive pressure (positive pressure ventilation or NCPAP) during initial hospitalization were evaluated in 266 inborn LBW infants (birth weight <1251 g). The data were categorized in three weight groups, <751, 751 to 1000 and 1001 to 1250 g and the incidence of BPD was computed in survivors based on oxygen need at 28 days, 36 weeks postmenstrual age (PMA) and the new severity of BPD criteria, that is, mild BPD: need for supplemental oxygen > or =28 days, but not at 36 weeks PMA; moderate BPD: need for supplemental oxygen > or =28 days and <30% at 36 weeks PMA and severe BPD: need for supplemental oxygen > or =28 days, and >30% at 36 weeks PMA and/or positive pressure at 36 weeks PMA. Further, BPD-associated comorbidities and short-term outcome data during hospitalization were compared among the groups, defined by severity of BPD. RESULTS: Among LBW infants <1251 g, the incidences of BPD at 28 days and 36 weeks PMA were 21.1 and 7.4% respectively. Using the newly defined criteria, the incidences of mild, moderate and severe BPD were 13.5, 4.8 and 2.6%, respectively. In total, 64.6% of these infants had mild BPD and 70.8% weighed <751 g at birth. Associated comorbidities correlated significantly with grades of underlying pulmonary disease. Also, significantly longer hospital stay, discharge at a higher PMA and lower growth velocity was observed with increasing grades of BPD. CONCLUSIONS: The new system for grading the severity of BPD offers a better description of underlying pulmonary disease and correlates with the infant's maturity, growth and overall severity of illness. Whether it will have a role in predicting long-term outcome remains to be determined.