Amniotic fluid interleukin‐18 at mid‐trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery

Thomakos, Nikolaos; Papapanagiotou, Angeliki; Παπαντωνίου, Ν.; Mesogitis, S.; Antsaklis, Aris

doi:10.1111/j.1471-0528.2009.02364.x

Cited by 27 publications

(20 citation statements)

References 22 publications

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“…For the fetus or neonate, infections with Ureaplasma are associated with a number of adverse outcomes, including chronic lung disease, pneumonias, cerebral white matter lesions, cerebral palsy and even death [4]; [5]. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, most likely triggered by the innate immune system [6]; [7]. It is believed that the innate immune response to these bacteria can lead to the activation of pattern recognition receptors (PRRs), production and release of pro-inflammatory mediators leading to the complications associated with preterm and term infants.…”

Section: Introductionmentioning

confidence: 99%

Synergic Activation of Toll-Like Receptor (TLR) 2/6 and 9 in Response to Ureaplasma parvum & urealyticum in Human Amniotic Epithelial Cells

et al. 2013

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Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), preterm labour (PL) pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs) in order to “sense” pathogens. One such family of PRRs are the Toll like receptor family (TLR). In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK) transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA), trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.

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Section: Introductionmentioning

confidence: 99%

Synergic Activation of Toll-Like Receptor (TLR) 2/6 and 9 in Response to Ureaplasma parvum & urealyticum in Human Amniotic Epithelial Cells

et al. 2013

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“…Functionally, both variants were linked with reduced IL-18 availability, evidenced by a progressive reduction in serum IL-18 levels in heterozygous and homozygous carriers in both patients and control women. These findings underscore the significance of reduced IL-18 levels in the maintenance of normal pregnancy (12,21), and in the pathogenesis of pregnancy complications (6,8,28), including RSM (21).…”

Section: Discussionmentioning

confidence: 72%

“…IL-18 promotes inflammation indirectly by stimulating IL-1b expression, which by structurally resembling IL-18, binds IL-18 receptors and thus potentiates proinflammation (2, 3) by engaging similar signaling and signal transduction (2,4). Alterations of IL-18 have been investigated in the susceptibility to autoimmune and inflammatory disorders (4,5), and changes in IL-18 levels have been linked with pregnancy complications, including preeclampsia (6,7), preterm delivery (8), IVF-ET failure (9), implantation failure (4,10), and recurrent miscarriage (10)(11)(12).…”

mentioning

confidence: 99%

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage

Al-Khateeb

Sater

Finan

et al. 2011

Fertility and Sterility

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“…Subsequently, several casecontrol studies have demonstrated an association between the amniotic fluid IL-6 concentration at the time of mid-trimester amniocentesis and preterm delivery [186, 191, 193]. The same has been reported for other cytokines [4, 20, 30, 102, 103, 139, 140, 186, 210]. A limitation of case control studies is that they are prone to biases.…”

Section: Introductionmentioning

confidence: 92%

Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery

Gervasi

Romero

Bracalente

et al. 2012

Journal of Perinatal Medicine

135

112

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Introduction Intra-amniotic inflammation is traditionally defined as an elevation of amniotic fluid interleukin (IL)-6. Previous case control studies have suggested an association between an elevated midtrimester amniotic fluid IL-6 and preterm delivery, although such an association has been recently challenged. Intra-amniotic inflammation can also be defined by an elevation of the T-cell chemokine, Interferongamma-inducible protein (IP)-10. An elevation in amniotic fluid IP-10 has been associated with chronic chorioamnionitis, a lesion frequently found in late spontaneous preterm birth and fetal death. In contrast, an elevation in amniotic fluid IL-6 is typically associated with acute chorioamnionitis and funisitis. This study was conducted to examine the relationship between an elevation in amniotic fluid IL-6 in the midtrimester and preterm delivery at or before 32 weeks of gestation, and the amniotic fluid concentration of IP-10 and preterm delivery after 32 weeks of gestation. Materials and methods This cohort study included 847 consecutive women undergoing genetic midtrimester amniocentesis; in 796 cases, amniotic fluid and pregnancy outcome was available for study after exclusion of abnormal karyotype and/or fetal congenital anomalies. Spontaneous preterm delivery was defined as early (≤ 32 weeks) or late (after 32 completed weeks of pregnancy). The amniotic fluid and maternal blood concentrations of IL-6 and IP-10 were measured by specific immunoassays. Results 1) The prevalence of preterm delivery was 8.3% (66/796), while those of early and late spontaneous preterm delivery were 1.5% (n = 12), and 4.5% (n = 36), respectively; 2) patients who had a spontaneous preterm delivery after 32 weeks of gestation had a higher median amniotic fluid IP-10 concentration than those who delivered at term [median 713 pg/mL, inter-quartile range (IQR) 509 – 1427 pg/mL vs. median 589 pg/mL, IQR 402 – 953 pg/mL; P = 0.006] and an elevation of amniotic fluid IP-10 concentration above 502 pg/mL (derived from an ROC curve) was associated with late spontaneous preterm delivery [odds ratio 3.9 (95% CI 1.6 – 9.9)]; 3) patients who had a spontaneous preterm delivery ≤ 32 weeks of gestation had a higher median amniotic fluid IL-6 concentration than those who delivered at term [median 2052 pg/mL, IQR 435 – 3015 pg/mL vs. median 414 pg/mL, IQR 209 – 930 pg/mL; P = 0.006], and an elevated amniotic fluid IL-6 concentration above 1740 pg/mL (derived from an ROC curve) was associated with early spontaneous preterm delivery [odds ratio 9.5 (95% CI 2.9 – 31.1)]; 4) subclinical intra-amniotic inflammation, defined as an elevation of IL-6 (≥ 2.9 ng/mL) or IP-10 (≥ 2.2 ng/mL) concentration above the 95th percentile of patients who had uncomplicated term delivery (n = 652 for IL-6 and n = 633 for IP-10), was observed in 6.3% (50/796) and 5.8% (45/770) of cases, respectively. Although each type of inflammation is a risk factor for spontaneous preterm delivery, many patients had a term delivery without complication; 5) the amniotic fluid ...

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Amniotic fluid interleukin‐18 at mid‐trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery

Cited by 27 publications

References 22 publications

Synergic Activation of Toll-Like Receptor (TLR) 2/6 and 9 in Response to Ureaplasma parvum & urealyticum in Human Amniotic Epithelial Cells

Synergic Activation of Toll-Like Receptor (TLR) 2/6 and 9 in Response to Ureaplasma parvum & urealyticum in Human Amniotic Epithelial Cells

Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage

Midtrimester amniotic fluid concentrations of interleukin-6 and interferon-gamma-inducible protein-10: evidence for heterogeneity of intra-amniotic inflammation and associations with spontaneous early (<32 weeks) and late (>32 weeks) preterm delivery

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