Postnatal Development of Hepatic Innate Immune Response

Rouzic, Valerie Le; Corona, Jennifer; Zhou, Heping

doi:10.1007/s10753-010-9265-5

Cited by 10 publications

(13 citation statements)

References 29 publications

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“…Accordingly, Kim et al [20] found that funisitis in preterm neonates is associated with a significantly higher fetal plasma IL-6 concentration compared to term neonates. The observation that umbilical cord serum concentration of LBP is higher in neonates with FIRS than in serum of children and adults with SIRS is also consistent with the finding that mRNA expression of LBP is higher in the liver of postnatal day 1 rats as compared to older animals [21]. …”

Section: Discussionsupporting

confidence: 85%

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

Pavcnik-Arnol

Lučovnik²,

Kornhauser‐Cerar³

et al. 2013

Neonatology

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Background: Intra-amniotic inflammation with preterm premature rupture of membranes (PPROM) is a risk factor for fetal inflammatory response syndrome (FIRS) and adverse neonatal outcome. Objectives: To evaluate the diagnostic accuracy of lipopolysaccharide-binding protein (LBP) for detecting FIRS in preterm neonates born after PPROM. Methods: This was a prospective study in the level III neonatal intensive care unit (42 neonates; 23 + 6 to 31 + 6 weeks' gestation) of mothers with PPROM. Umbilical cord blood concentrations of LBP, C-reactive protein (CRP), interleukin (IL)-6 and white blood cell count with differential were measured at delivery and 24 h after birth. Neonates were classified into FIRS (n = 22) and no FIRS (n = 20) groups according to clinical criteria and IL-6 level (≥17.5 pg/ml). Histological examination of the placenta and umbilical cord was performed. Neurological examination at 12 months' corrected age was performed. Results: Umbilical cord blood concentration of LBP was significantly higher in the FIRS group than in the no FIRS group at delivery (median 21.6 mg/l vs. median 2.3 mg/l; p < 0.0001) and 24 h after birth (median 17.2 mg/l vs. median 20.0 mg/l; p < 0.001). The area under the ROC curve for FIRS at delivery was 0.98 (95% CI 0.88-1.0) for LBP, 0.92 (95% CI 0.80-0.99) for CRP and 0.82 (95% CI 0.64-0.94) for immature to total neutrophil ratio. Similar results were obtained if FIRS was defined by funisitis. Umbilical cord blood concentration of LBP at delivery was significantly higher in neonates with abnormal neurological exam at 12 months than in those with normal exam (median 19.5 mg/l vs. median 3.75 mg/l; p < 0.015). Conclusions: In preterm neonates born to asymptomatic women with PPROM, LBP in cord blood at delivery is an excellent diagnostic biomarker of FIRS/funisitis with prognostic potential.

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Section: Discussionsupporting

confidence: 85%

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

Pavcnik-Arnol

Lučovnik²,

Kornhauser‐Cerar³

et al. 2013

Neonatology

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“…Clearly, it would be interesting to learn if this sexual dimorphism is swiftly detectable in vivo. However, as shown by our data and others, the diverse bacteria and times postinfection [ 31 ] are factors that cause significant variability in MIP-1β and that cannot readily be controlled for in human infections, likely hindering the recognition of sex differences in MIP-1β secretion in the context of perinatal infections. Hence, besides the current ex vivo experiments, further clues about the importance of MIP-1β in sex-specific responses may be gained using mouse models of perinatal infection, e.g., with S. aureus .…”

Section: Discussionmentioning

confidence: 62%

Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro

Reuschel

Toelge

Haeusler

et al. 2020

IJMS

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During pregnancy, infections caused by the gram-positive bacteria Enterococcus faecalis (E. faecalis), Streptococcus agalacticae (S. agalacticae), and Staphylococcus aureus (S. aureus) are major reasons for preterm labor, neonatal prematurity, meningitis, or sepsis. Here, we propose cytokine responses to bacterial infections by the immature perinatal immune system as central players in the pathogenesis of preterm birth and neonatal sepsis. We aimed to close the gap in knowledge about such cytokine responses by stimulating freshly isolated umbilical blood mononuclear cells (UBMC) with lysates of E. faecalis, S. agalacticae, and S. aureus collected from pregnant women in preterm labor. Bacterial lysates and, principally, S. aureus and S. agalacticae distinctly triggered most of the eleven inflammatory, anti-inflammatory, TH1/TH2 cytokines, and chemokines quantified in UBMC culture media. Chemokines depicted the most robust induction. Among them, MIP-1β was further enhanced in UBMC from female compered to male newborn infants. Due to its stability and high levels, we investigated the diagnostic value of IL-8. IL-8 was critically upregulated in cord blood of preterm neonates suffering from infections compared to gestational age-matched controls. Our results provide novel clues about perinatal immunity, underscoring a potential value of IL-8 for the timely detection of infections and suggesting that MIP-1β constitutes an early determinant of sex-specific immunity, which may contribute, e.g., to male’s vulnerability to preterm birth.

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“…There are few reports that describe whether this situation also occurs similarly in the liver. For instance, Le Rouzic et al found that the hepatic innate immunity is suppressed in the p1 neonatal mice compared with juveniles (p21) and adults (p70) by measuring basal TLR4, CD14 , and MD2 gene expression in rats ( 63 ). Furthermore, Nakagaki et al reported a significant higher Tlr4, Itgam (CD11b, macrophage marker), and a reduced Nr1h3 (NR1, regulator of macrophage function) hepatic gene expression in the neonatal mice when exposed to LPS ( 64 ) indicating an insufficient innate immunity maturation.…”

Section: Discussionmentioning

confidence: 99%

Maturation of the Acute Hepatic TLR4/NF-κB Mediated Innate Immune Response Is p65 Dependent in Mice

et al. 2020

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Compared to adults, neonates are at increased risk of infection. There is a growing recognition that dynamic qualitative and quantitative differences in immunity over development contribute to these observations. The liver plays a key role as an immunologic organ, but whether its contribution to the acute innate immune response changes over lifetime is unknown. We hypothesized that the liver would activate a developmentally-regulated acute innate immune response to intraperitoneal lipopolysaccharide (LPS). We first assessed the hepatic expression and activity of the NF-κB, a key regulator of the innate immune response, at different developmental ages (p0, p3, p7, p35, and adult). Ontogeny of the NF-κB subunits (p65/p50) revealed a reduction in Rela (p65) and Nfkb1 (p105, precursor to p50) gene expression (p0) and p65 subunit protein levels (p0 and p3) vs. older ages. The acute hepatic innate immune response to LPS was associated by the degradation of the NF-κB inhibitory proteins (IκBα and IκBβ), and nuclear translocation of the NF-κB subunit p50 in all ages, whereas nuclear translocation of the NF-κB subunit p65 was only observed in the p35 and adult mouse. Consistent with these findings, we detected NF-κB subunit p65 nuclear staining exclusively in the LPS-exposed adult liver compared with p7 mouse. We next interrogated the LPS-induced hepatic expression of pro-inflammatory genes (Tnf, Icam1, Ccl3, and Traf1), and observed a gradually increase in gene expression starting from p0. Confirming our results, hepatic NF-κB subunit p65 nuclear translocation was associated with up-regulation of the Icam1 gene in the adult, and was not detected in the p7 mouse. Thus, an inflammatory challenge induces an NF-κB-mediated hepatic innate immune response activation across all developmental ages, but nuclear translocation of the NF-κB subunit p65 and associated induction of pro-inflammatory genes occurred only after the first month of life. Our results demonstrate that the LPS-induced hepatic innate immune response is developmentally regulated by the NF-κB subunit p65 in the mouse.

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Postnatal Development of Hepatic Innate Immune Response

Cited by 10 publications

References 29 publications

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes

Perinatal Gram-Positive Bacteria Exposure Elicits Distinct Cytokine Responses In Vitro

Maturation of the Acute Hepatic TLR4/NF-κB Mediated Innate Immune Response Is p65 Dependent in Mice

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