Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response

Tamara Stampalija, Roberto Romero, Steven J. Korzeniewski, Piya Chaemsaithong, Jezid Miranda, Lami Yeo, Zhong Dong, Sonia S. Hassan, Tinnakorn Chaiworapongsa

Research output: Contribution to journalArticle

Abstract

Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS. Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration ≥17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay. Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8-80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6-20.1 ng/mL; p <0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1-75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9-23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman's Rho = 0.7, p <0.0001). Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.

Original languageEnglish
Pages (from-to)1384-1393
Number of pages10
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume26
Issue number14
DOIs
Publication statusPublished - Sep 2013

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Chorioamnionitis
Umbilical Cord
Anti-Inflammatory Agents
Extremities
Interleukin-10
Th1-Th2 Balance
Cytokines
Premature Obstetric Labor
Rupture
Interleukin-6
Inflammation
Membranes
Enzymes
Infection

Keywords

  • Funisitis
  • IL-10
  • Inflammation
  • Intra-amniotic infection/inflammation
  • Preterm labor

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynaecology

Cite this

Soluble ST2 in the fetal inflammatory response syndrome : in vivo evidence of activation of the anti-inflammatory limb of the immune response. / Stampalija, Tamara; Romero, Roberto; Korzeniewski, Steven J.; Chaemsaithong, Piya; Miranda, Jezid; Yeo, Lami; Dong, Zhong; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn.

In: Journal of Maternal-Fetal and Neonatal Medicine, Vol. 26, No. 14, 09.2013, p. 1384-1393.

Research output: Contribution to journalArticle

Stampalija, Tamara ; Romero, Roberto ; Korzeniewski, Steven J. ; Chaemsaithong, Piya ; Miranda, Jezid ; Yeo, Lami ; Dong, Zhong ; Hassan, Sonia S. ; Chaiworapongsa, Tinnakorn. / Soluble ST2 in the fetal inflammatory response syndrome : in vivo evidence of activation of the anti-inflammatory limb of the immune response. In: Journal of Maternal-Fetal and Neonatal Medicine. 2013 ; Vol. 26, No. 14. pp. 1384-1393.
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abstract = "Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS. Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration ≥17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay. Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8-80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6-20.1 ng/mL; p <0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1-75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9-23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman's Rho = 0.7, p <0.0001). Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.",
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author = "Tamara Stampalija and Roberto Romero and Korzeniewski, {Steven J.} and Piya Chaemsaithong and Jezid Miranda and Lami Yeo and Zhong Dong and Hassan, {Sonia S.} and Tinnakorn Chaiworapongsa",
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T2 - in vivo evidence of activation of the anti-inflammatory limb of the immune response

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AU - Romero, Roberto

AU - Korzeniewski, Steven J.

AU - Chaemsaithong, Piya

AU - Miranda, Jezid

AU - Yeo, Lami

AU - Dong, Zhong

AU - Hassan, Sonia S.

AU - Chaiworapongsa, Tinnakorn

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N2 - Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS. Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n = 36), and without funisitis (n = 30). FIRS (umbilical cord IL-6 concentration ≥17.5 pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay. Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6 ng/mL, interquartile range (IQR) 13.8-80.3 ng/mL versus median 6.7 ng/mL, IQR 5.6-20.1 ng/mL; p <0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1 ng/mL; IQR 7.1-75.0 ng/mL versus median 7.2 ng/mL; IQR 5.9-23.1 ng/mL; p = 0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman's Rho = 0.7, p <0.0001). Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.

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KW - Funisitis

KW - IL-10

KW - Inflammation

KW - Intra-amniotic infection/inflammation

KW - Preterm labor

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