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1337 Newborn and Adult Monocytes Show Different Inflammatory Responses to Bacterial Infection: Potential Role of MAPK Inhibition
  1. EM Speer,
  2. AJ Chander
  1. Pediatrics, Stony Brook University, Stony Brook, NY, USA

Abstract

Background and Aims The neonatal inflammatory response is associated with adverse outcomes like chronic lung disease. Recent studies suggested that newborn innate immune responses differ from adults. We aim to compare the expression of inflammatory cytokines between newborn and adult monocytes, and to investigate the mechanisms underlying the differential response.

Methods Purified monocytes from 15 healthy term newborns (C-section, no labor or chorioamnionitis) and 15 healthy adults (no infection), were cultured (90min) and stimulated without or with 0.1ng/ml or 10ng/ml LPS for 4 or 24 hours. Cells were harvested and RNA extracted. mRNA expression was determined with real-time PCR and normalized to β2-microglobulin as housekeeping gene. Results were analyzed by ANOVA and Students t-test with p≤0.05 considered significant.

Results Results are discussed in comparison to control values. Newborn monocytes showed increased IL6 (0.1ng/ml or 10ng/ml LPS) and TNFα (0.1ng/ml LPS) expression after 4h, whereas IL10mRNA was lower after 4h and 24h LPS compared to adults. LPS-stimulation increased NFKBp65 expression in adults but not in newborns at 24h. IKBα and Toll-interacting protein were comparable between groups. IRAK3 (TLR4-pathway regulator) was elevated in newborns at 4 and 24h with LPS-stimulation, but only at 24h in adults. Dual specificity phosphatase 1 (DUSP1) was significantly lower in newborn monocytes compared to adults after 24h LPS at both concentrations.

Conclusions Newborn compared to adult monocytes show increased expression of inflammatory cytokines. Diminished upregulation of DUSP1 (negative regulator of MAPK-pathway) might explain the enhanced pro-inflammatory profile of newborn compared to adult monocytes after microbial stimulation.

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