Amniotic fluid IL-6 in preterm labour: association with infection

Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06510.
Journal of Clinical Investigation (Impact Factor: 13.77). 06/1990; 85(5):1392-400. DOI: 10.1172/JCI114583
Source: PubMed

ABSTRACT To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL-6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P < 0.0001). The 23-25- and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-μl aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P < 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor.

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Available from: Pravin Sehgal, Oct 09, 2014
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    • "While available evidence suggests that healthy pregnancy is typified by an enhanced inflammatory state, studies also show that excessive inflammation is incompatible with healthy pregnancy. Elevations in proinflammatory cytokines in maternal serum and amniotic fluid are causally implicated in risk of preterm delivery in the context of infection as well as idiopathic cases [10] [11] [12] [13] [14]. Proinflammatory cytokines can promote preterm labor by triggering preterm contractions, encouraging cervical ripening, and causing rupture of the membranes [15] [16]. "
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    ABSTRACT: The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated.
    Cytokine 07/2014; 70(2). DOI:10.1016/j.cyto.2014.06.018 · 2.87 Impact Factor
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    • "In the event of preterm birth associated with intraamniotic infection, maternal serum IL6 is higher than in normal labour (Stallmach et al., 1995). Preterm birth is also associated with elevated amniotic fluid IL6 regardless of infection, although levels are higher in women where infection is evident (Romero et al., 1990; Silver et al., 1993; Menon et al., 1995). An altered balance in IL6 trans-signalling regulators in several aetiologies of preterm birth was suggested recently by a large study that showed increased amniotic fluid levels of IL6 and sIL6R in cases involving intra-amniotic inflammation, and decreased levels of sgp130 in women with premature preterm rupture of membranes, independent of intra-amniotic inflammation . "
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    ABSTRACT: IL6 is a multifunctional cytokine with pivotal roles in the inflammatory response and in directing T cell differentiation in adaptive immunity. IL6 is widely expressed in the female reproductive tract and gestational tissues, and exerts regulatory functions in embryo implantation and placental development, as well as the immune adaptations required to tolerate pregnancy. Here, we summarise the current understanding of how membrane-bound and soluble receptors mediate IL6 signalling to regulate leukocytes and non-haemopoietic cells. We review the published literature regarding the expression and actions of IL6 in the uterus, decidua and placenta, and studies implicating this cytokine in pregnancy disorders. Elevated IL6 is frequently evident in the altered cytokine profiles characteristic of unexplained infertility, recurrent miscarriage, preeclampsia and preterm delivery. Notably, there is compelling evidence indicating altered systemic IL6 trans-signalling in women prone to recurrent miscarriage, with excessive IL6 bioavailability potentially inhibiting generation of CD4+ T regulatory cells required for pregnancy tolerance. Insufficient local IL6 may also contribute to fetal loss, since IL6 expression is reduced in the endometrium of women with recurrent miscarriage, and in the fetal-placental tissue of CBA×DBA/2 mice. Consistent with the role of IL6 in key reproductive events, Il6 null mutant mice exhibit elevated fetal resorption and delayed parturition. Investigation of the association between IL6 signalling components and T cell responses in pregnant women, as well as detailed analysis of the maternal immune response in IL6-deficient mice, is now required to define the mechanisms by which this cytokine exerts influence on reproductive success.
    Journal of Reproductive Immunology 07/2012; 95(1-2):1-14. DOI:10.1016/j.jri.2012.05.004 · 2.37 Impact Factor
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    • "IL-1, the first cytokine implicated, is up-regulated in response to microbial products in the human decidua, resulting in the production of prostaglandins by the amnion and deciduas (Romero, Brody et al. 1989a; Romero, Durum et al. 1989b; Romero, Wu et al. 1989c). Mid-trimester amniotic fluid levels of IL-1 levels are associated positively with preterm delivery (Puchner, Iavazzo et al. 2011), and IL-6 concentrations in amniotic fluid are considered a marker for infection (Romero, Avila et al. 1990; Yoon, Romero et al. 1995). Other cytokines including IL-10 (Gotsch, Romero et al. 2008), TNF (Romero, Manogue et al. 1989d), colony stimulating factor (CSF) (Saito, Kato et al. 1992) and IL-18 (Pacora, Romero et al. 2000) among others have been linked to infection associated preterm labour. "
    Recent Advances in Research on the Human Placenta, 03/2012; , ISBN: 978-953-51-0194-9
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