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102: The immediate postnatal period is characterized by an increased sensitivity of the neonate to E. coli endotoxin

      Objective

      Neonatal inflammation represents a highly orchestrated process designed to combat infection and tissue injury. Although pro-inflammatory cytokines are essential for neonatal defense against Gram (-) infection, exaggerated cytokine production has deleterious effects. The present study addressed the question whether in comparison to the adult, the immediate postnatal period represents a life phase characterized by deficiency in the adaptive immune response to infection.

      Study Design

      Paired, time-matched whole blood maternal-cord blood samples were obtained from 33 normal full-term pregnant women who had a clinically indicated Cesarean delivery in the absence of labor. Maternal and cord blood was collected under sterile conditions and incubated ex vivo with 1 μg/ml E. coli LPS (LPS) in a CO2 thermostat at 37C for 1,3,6,12&24h. In addition, we studied the immune response of maternal and cord blood in response to rsLPS (LPS competitive antagonist). Interleukin-6 (activator of acute phase responses) was measured by ELISA.

      Results

      1) There were significant differences in the response of the maternal vs. neonatal cord blood to LPS despite lack of differences in cytokine levels in unstimulated conditions; 2) LPS elicited a significant IL-6 response at 1h of incubation in both maternal and neonatal blood; 3) Both maternal and neonatal blood continued to respond to LPS challenge up to 6 hours and plateaued thereafter; 4) At all times, the neonatal blood responded more robustly to LPS compared to maternal blood (P<0.001); 5) rsLPS elicited an inhibitory response (antagonist) in maternal blood, but a stimulatory effect (agonist) in neonatal compartment.

      Conclusion

      We provide evidence that the neonate has a heightened sensitivity to endotoxin in the immediate postnatal period. The divergent effect of rsLPS suggests that the maternal and neonatal LPS recognition components (TLR4, CD14, MD2) may be functionally different.
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