Fetal and early neonatal interleukin-6 response

Chiesa, Claudio; Pacifico, Lucia; Natale, Fabio; Hofer, Nora; Osborn, John; Resch, Bernhard

doi:10.1016/j.cyto.2015.03.015

Cited by 65 publications

(72 citation statements)

References 132 publications

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“…The neonate has emerged from an intrauterine environment aimed specifically against developing pro-inflammatory responses(22–24). The cytokine milieu of the neonate is considerably different from adults(25), and is largely under the control of negative signaling to prevent an over-exuberant response to commensal or environmental organisms(22, 24). Roger et al(22) noted that releasing the immune system from these immunosuppressive pathways improved both cytokine responses and cellular responses to bacteria.…”

Section: Discussionmentioning

confidence: 99%

Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates

Young

Fallon

Heffernan

et al. 2017

Surgery

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Introduction Sepsis and the ensuing immune dysfunction, continues to be a major contributor to neonatal morbidity and mortality. Neonatal sepsis also is associated with profound immune dysfunction. We have recently identified a role for a family of co-inhibitory molecules that are altered in murine sepsis and in critically ill adult patients, which may be a target for development of novel therapies. There is, however, a paucity of data pertaining to the role of co-inhibitory check point proteins in the control and modulation of neonatal sepsis. Methods The cecal slurry (CS) model consists of harvesting the cecal contents of an adult wild type (Wt) male mouse and combining it with 5% dextrose to create a cecal slurry (CS) with a concentration of 80mg/ml (LD70 at 7 days). Neonatal mice (5–7 days of age) underwent intraperitoneal injection (IP) of the CS or IP of 0.9% saline for sham procedure (Sh). Wild Type (C57BL/6) or PD-1−/− mice were used. 7 day survival study was undertaken. Cytometric bead array was used for cytokine expression. Blood and peritoneal fluid was cultured for bacterial burden. Flow cytometry was used to assess the peritoneal cavity cell populations. Results There was no mortality following Sh in either WT or PD-1−/− pups. PD-1 markedly affected sepsis survival with significantly improved survival in the PD-1−/− pups (40% versus 80%; p<0.01). This survival improvement was not associated with any difference in bacterial clearance. The bacterial burden was equivalent between WT and PD-1−/− pups at 24 hours following CS. However, PD-1−/− pups did display an increased circulating cytokine response to the CS compared with WT, with increased expression of IL-6, IL-10 and TNF-α levels. Within the peritoneal cavity, sepsis induced an influx of neutrophils, a finding that was increased in PD-1−/− pups. Although the T-cell response was unaffected by PD-1, it was noted that CS induced a loss of peritoneal B-cells in WT, while the peritoneal B-cell population was preserved in PD-1−/− pups. Conclusion Our data suggests that the checkpoint protein, PD-1, plays an important role in controlling the immune response to sepsis in the neonate, ultimately affecting sepsis related mortality in this neonatal murine model of sepsis. Akin to adult studies, this data further emphasizes the potential therapeutic target for PD-1 across a spectrum of septic patients.

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Section: Discussionmentioning

confidence: 99%

Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates

Young

Fallon

Heffernan

et al. 2017

Surgery

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“…IL-1β and IL-6 are pleiotropic cytokines that are produced by a variety of cells in response to infection and tissue injury. The body of literature regarding the use of AF concentrations of IL-6 as a biomarker for the fetal inflammatory response syndrome that leads to early onset neonatal sepsis and white matter injury in neonates has grown rapidly [12] . In this study, we demonstrated that AF IL-1β and IL-6 were significantly higher in class II-III obese women than in other groups.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Body Mass Index on Second-Trimester Amniotic Fluid Cytokine and Matrix Metalloproteinase Levels

Melekoğlu

Çiftçi²,

Eraslan³

et al. 2017

Gynecol Obstet Invest

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Aim: The aim of this study was to determine the effects of obesity on amniotic fluid (AF) inflammatory markers in second-trimester AF, testing the hypothesis that there is a relationship between maternal body mass index (BMI) and fetal inflammatory exposure. Methods: AF was obtained from 84 singleton pregnant women undergoing elective amniocentesis for karyotype analysis at 16-24 weeks of gestation between April 2014 and May 2016. The cell-free AF was used to analyze interleukin (IL)-1β and IL-6, and matrix metalloproteinase (MMP)-1, MMP-6, and MMP-13. Results: IL-1β levels were significantly higher in class II-III obese patients than in class I obese, overweight, and normal weight patients (14.68 ± 1.37 vs. 13.34 ± 1.86 vs. 13.00 ± 2.22 vs. 10.78 ± 1.92, respectively; p < 0.05). IL-6 levels were lowest in the normal weight group and highest in class II-III obese patients. MMP-1, MMP-6, and MMP-13 levels were also significantly higher in class II-III obese patients than in the other groups. Conclusion: This study demonstrated that the fetuses of class II-III obese women are exposed in utero to higher cytokine and MMP levels than fetuses of lean women. Modification of current cutoff levels of intra-amniotic cytokines and MMPs according to the BMI could improve the accuracy of the prenatal diagnosis of intra-amniotic infection and inflammation.

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“…In the present study, we did not find significant differences in IL‐6 concentrations. One possible reason for the absence of changes in IL‐6 levels may be related to the fact that we have excluded neonates with confirmed or suspected sepsis, while, in other studies, babies with sepsis were included [15, 16, 24, 44, 45]. IL‐6 is a proinflammatory cytokine that increases in case of sepsis [44, 45].…”

Section: Discussionmentioning

confidence: 99%

“…One possible reason for the absence of changes in IL‐6 levels may be related to the fact that we have excluded neonates with confirmed or suspected sepsis, while, in other studies, babies with sepsis were included [15, 16, 24, 44, 45]. IL‐6 is a proinflammatory cytokine that increases in case of sepsis [44, 45]. The release of IL‐6 triggers an inflammatory cascade secondary to infection, with consequent developmental delay and/or brain injury [44, 46, 47].…”

Section: Discussionmentioning

confidence: 99%

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Urinary Levels of IL-1β and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study

Magalhães

Moreira

Vieira

et al. 2017

Mediators of Inflammation

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Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1β, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1β and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

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Fetal and early neonatal interleukin-6 response

Cited by 65 publications

References 132 publications

Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates

Improved survival after induction of sepsis by cecal slurry in PD-1 knockout murine neonates

The Effects of Body Mass Index on Second-Trimester Amniotic Fluid Cytokine and Matrix Metalloproteinase Levels

Urinary Levels of IL-1β and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study

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