Inflammatory Response In Women Research Articles

Diagnostic tests for the prediction of histological chorioamnionitis and funisitis in pregnant women with preterm premature rupture of membranes: A systematic review.

Infection of the amniotic cavity is an important driver and/or consequence of preterm prelabour rupture of membranes (PPROM). Prediction of infection is challenging, limiting guidance for interventions during the antenatal period. Infection typically triggers a host inflammatory response, and non-invasive indirect markers of the maternal or fetal inflammatory response have been reported in the context of PPROM and intra-amniotic infection. Some of these markers have also been tested in amniotic fluid (AF) samples. This study compared markers of the inflammatory response in women with PPROM against the outcome standard of histological chorioamnionitis (HCA) or funisitis (FUS). Searches were conducted for studies reporting diagnostic test sensitivity and specificity for proven HCA or FUS in pregnant women with PPROM after 20 weeks' gestation. Weighted mean pooled sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, diagnostic odds ratio and 95% confidence intervals were calculated for each of the selected diagnostic tests. Except ultrasonographic detection of fetal thymic involution, almost all index tests analysed showed relatively low sensitivity. Maternal white cell count, interleukin-6 (IL-6) and AF IL-6 had credible specificity. Testing of AF markers, while more consistent than serum markers, showed no clear diagnostic accuracy improvement. There is a clear lack of evidence for the reliability of any individual diagnostic test to assist in the detection of HCA or FUS in women with PPROM. Combining several markers into a predictive model for improved diagnosis may be worth investigating.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles.

To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

RANTES and developmental defects of enamel in children: A Brazilian prenatal cohort (BRISA).

Little is known about the effect of maternal immunological factors on the etiology of developmental defects of enamel (DDE). RANTES (Regulated on Activation Normal T Cell Expressed and Secreted) is a chemokine produced by fibroblasts, lymphoid and epithelial mucosa cells in response to various external stimuli. Despite its importance for embryogenesis, RANTES expression has been demonstrated in multiple diseases characterized by inflammation, tumor and immune response, and wound healing. We hypothesized that altered levels of RANTES during pregnancy are associated with the immune and inflammatory response in women, which could lead to the occurrence of DDE in utero (DDE-iu), directly or mediated by preterm birth. Therefore, this study aimed to evaluate the direct and indirect effects of serum levels of RANTES in pregnant women in the occurrence of DDE-iu in children. This is a longitudinal case-control study. The mothers and their children (327) were evaluated in three moments: prenatal care, post childbirth, and when the child was between 12.3 and 36 months of age. The analysis was performed with structural equation modeling, estimating the standardized coefficient (SC), adopting α = 5%. There was a direct and negative effect of RANTES on the outcome (SC = -0.137; p = 0.022). This association was not mediated by preterm birth (SC = 0.007; P = 0.551). When considering the specific types of DDE-iu, RANTES had a direct effect on hypoplasia (SC = -0.190; p = 0.007), but not on opacity (SC = 0.343; p = 0.074). Lower serum levels of RANTES may contribute to a higher number of teeth with DDE-iu, specifically hypoplasia. However, more evidence supported by clinical, laboratory and epidemiological studies is still needed.

Evaluation of cytokine profile in cervicovaginal lavage specimens of women having asymptomatic reproductive tract infections

Reproductive tract infections (RTIs) such as vaginal candidiasis and bacterial vaginosis (BV) are common among sexually active women and can be both symptomatic or asymptomatic. The microbiota of the reproductive tract triggers immune response at the cervicovaginal interface resulting in secretion of cytokines during the course of these RTIs. The objective of this study was to evaluate the cytokine profile in cervicovaginal lavage of women having asymptomatic vaginal infections. Measurement of vaginal cytokines was done for various interleukins including IL-1β, IL-6, IL-8, IL-10, IL-12/IL23p40, IL-17A, tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) by ProcartaPlex™ Multiplex Immunoassay. Women having vaginal Candida infection had increased concentration of IL-1β (p=.01), IL-6 (p=.007), IL-8 (p=.327), IL-12/IL23p40 (p=.049) and IFN-γ (p=.125). The results of our study suggest that evaluation of these cytokines could be explored as an additional measure to determine host inflammatory response in women having asymptomatic vaginal candidiasis. Impact Statement What is already known on this subject? Studies assessing the vaginal cytokine profile to assess the vaginal milieu in various cohorts such as post-menopausal women, pregnant women, women with history of preterm birth, CIN and scheduled IVF cycle are being undertaken. Variable cytokine response has been reported in literature in women with symptomatic bacterial vaginosis and Candida infection. However, much less is known about vaginal cytokine profile in asymptomatic infection. What do the results of this study add? The results of the study show increased concentration of the pro-inflammatory cytokines IL-1β, IL-6 IL-8, IL-12/IL23p40 and interferon gamma (IFN-γ) in women having asymptomatic Candida, vaginal leucocytosis and raised vaginal pH. What are the implications of these findings for clinical practice and/or further research? Evaluation of vaginal cytokine profile (IL-1β, IL-6 IL-8, IL-1β, IL-12/IL23p40 and IFN-γ) could be explored as an additional measure to determine inflammation in asymptomatic women. Vaginal cytokines (IL-1β, IL-6 IL-8, IL-1β, IL-12/IL23p40 and IFN-γ) could be used further for development of a point of care test.

Sex differences in cytokine profiles during suppressive antiretroviral therapy.

Despite lower plasma HIV RNA levels, women progress faster to AIDS than men. The reasons for these differences are not clear but might be a consequence of an elevated inflammatory response in women. We investigated sex differences in cytokine profiles by measuring the concentrations of 36 cytokines/chemokines by Luminex in blood of women and men (sex at birth) with chronic HIV infection under suppressive therapy. We initially performed a principal component analysis to see if participants clustered by sex, and then fit a partial least squares discriminant analysis (PLS-DA) model where we used cytokines to predict sex at birth. The significance of the difference in nine cytokines with VIP greater than 1 was tested using Wilcoxon test-rank. Further, potential confounding factors were tested by multivariate linear regression models. Overall, we predicted sex at birth in the PLS-DA model with an error rate of approximately 13%. We identified five cytokines, which were significantly higher in women compared with men, namely the pro-inflammatory chemokines CXCL1 (Gro-α), CCL5 (RANTES), CCL3 (MIP-1α), CCL4 (MIP-1β), as well as the T-cell homeostatic factor IL-7. The effect of sex remained significant after adjusting for CD4 + , age, ethnicity, and race for all cytokines, except for CCL3 and race. The observed sex-based differences in cytokines might contribute to higher immune activation in women compared with men despite suppressive therapy. Increased levels of IL-7 in women suggest that homeostatic proliferation may have a differential contribution to HIV reservoir maintenance in female and male individuals. Our study emphasizes the importance of sex-specific studies of viral pathogenesis.

Host inflammatory response in women with vaginal epithelial abnormalities after pessary use.

Vaginal epithelial abnormalities (VEA) are a common complication associated with pessary use. The objective of this study was to determine if there is a host pro-inflammatory response associated with pessary use and VEA. Patients wearing pessaries for at least two weeks for the management of pelvic organ prolapse and/or urinary incontinence were screened for eligibility. Vaginal swabs were collected from women with VEA (cases) and without VEA (controls). Cases were matched to controls in a 1:3 ratio. Cytokine analysis of the collected samples was performed using multiplex analysis to determine the concentrations of interleukin (IL)6, interferon alpha 2 (IFNα2), tumor necrosis factor alpha (TNFα) and IL1β. A cross-sectional analysis was performed, comparing vaginal cytokine concentrations in women with and without VEA. We enrolled 211 patients in this analysis: 50 cases and 161 controls. The median concentrations (pg/mL) of the four cytokines for cases and controls respectively were; IL6: 6.7 (IQR <2.9 [the lower limit of detection, LLD]-14.2) and < 2.9 (LLD) (IQR <2.9 [LLD]-5.5), IFNα2: 8.2 (IQR 6.1-13.9) and 7.9 (IQR 3.9-13.6), TNFα: 15.2 (IQR 6.1-30.4) and 4.68 (IQR <2.3 [LLD]-16.3), IL1β 195.7 (IQR 54.5-388.6) and 38.5 (IQR 6.7-154.9). The differences in median cytokine levels were statistically higher in cases for IL6, TNFα, and IL1β (all p< 0.001) compared to controls. Older age (OR: 1.062, 95% CI, 1.015-1.112), lower BMI (OR: 0.910, 95% CI, 0.839-0.986) and presence of VEA at last check (OR: 5.377, 95% CI, 2.049-14.108) were associated with higher odds of having VEA on multivariate analysis. Pro-inflammatory cytokines, specifically IL6, TNFα, and IL1β, are elevated in pessary-wearing patients who have VEA. Additional prospective studies are needed to assess baseline vaginal inflammatory profiles before and after pessary placement to understand VEA formation in pessary patients.

Immune-mediated mechanisms of the inflammatory response in women with combined infections of the lower genital tract

Aim: to increase the effectiveness of combination therapy and reduce frequency of recurrences of inflammatory diseases in the lower genital tract of combined etiology.Materials and Мethods. There was conducted a prospective, randomized, blind, comparative clinical study. 80 women with vaginal microbiota disorders were examined randomized into 2 groups: group I (n = 40) – antibiotic therapy was carried out in combination with the preparation Superlimph, group II (n = 40) – a standalone antibacterial therapy; group III consisted of 20 patients lacking gynecological diseases considered to provide with control laboratory parameters. Clinical and laboratory methods were used: microscopy of vaginal smears, detection of viruses and sexually transmitted infections, measurement of serum cytokine levels – interleukins (IL-1â, IL-2, IL-4, IL-6, IL-8, IL-10), tumor necrosis factor alpha, (TNF-á), interferon gamma (IFN-ã).Results. It was found that clinical recovery occurred in 90.0 and 70.0 % of patients in group I and group II (р = 0.02), respectively. Microbiological recovery was observed in 100.0 and 67.5 % of patients, respectively (р = 0.003). In group I, the isolation of herpes simplex virus type 2 was found in 80.0 and 45.2 % of patients before and after treatment (p &lt; 0.001), respectively, whereas in group II – in 82.5 and 77.5 %, respectively (p = 0.58), between groups – p &lt; 0.001. Before treatment the level of all cytokines, excepting IFN-ã, was higher than the reference values in both groups: in group I, their magnitude decreased after treatment (p &lt; 0.001) and corresponded to the reference values; in group II no changes occurred. Three months after treatment, no relapses were observed in group I, whereas frequency of relapses in group II was 22.5 %, within 1 year – 0 and 35.1 %, respectively. Predictors of recurrent dysbiosis (IL-2, IL-6 and TNF-á in increased concentrations after a course of treatment) were identified.Conclusion. Treatment with a combined broad-spectrum antimicrobial drug along with topical immunomodulatory agent containing exogenous cytokines is an effective strategy for treating concomitant dysbiosis and preventing relapse.

Correlation of NUCB2/Nesfatin-1 with Cytokine Levels in Primary Open-Angle Glaucoma.

PurposeNesfatin-1 is produced in various tissues of the body including the hypothalamus. Neuroprotective properties of the neuropeptide hormone Nesfatin-1 were recently described. The aim of the study was to analyze the molecule Nesfatin-1 as a possible biomarker in POAG with neuroprotective properties pointing out the retinal-hypothalamic axis as target site in POAG and to obtain a molecular signature of cytokines in POAG as neuroinflammatory processes are a key factor of glaucoma development.MethodsIn this study, n=35 patients with moderate and advanced POAG (mean age 65.0y, IOP 13.9±3.0mmHg) and n=35 healthy controls (mean age 51.6y, IOP 14.3±2.7mmHg) were included. Clinical parameters including IOP, cup to disc ratio (CDR), glaucoma medication and retinal nerve fiber layer thickness (RNFL) were recorded. Plasma was collected for NUCB2/nesfatin-1 measurement using a Nesfatin-1 ELISA and for detection of 13 inflammatory cytokines using a multiplex bead-based immunoassay (MagPix). Multiple linear regression analysis was performed to adjust for confounding factors.ResultsSex-independent or sex-dependent variables showed no significant differences in the Nesfatin-1 level (p>0.05). As a trend, an increase in NUCB2/nesfatin-1 in male glaucoma patients was found. Increased concentrations of 11 cytokines (GM-CSF, Interferon-γ, Interleukin-1β, IL-2, 4, 5, 6, 7, 10, 12 and TNF-α) were detected in POAG. The female glaucoma patients demonstrated elevated cytokine concentrations compared to male patients. NUCB2/nesfatin-1 showed a significant correlation to IL-2 and IL-13 levels in POAG. Stepwise multiple regression analysis showed no difference in NUCB2/nesfatin-1 level between POAG and healthy controls after adjusting for sex and age (all p>0.05).ConclusionAs a trend, male POAG patients showed increased plasma NUCB2/nesfatin-1 levels. We further found inflammation as contributing factor to the pathogenesis of glaucoma, with a greater inflammatory response in women.

Porphyromonas gingivalis Placental Atopobiosis and Inflammatory Responses in Women With Adverse Pregnancy Outcomes.

The microbiome modulates inflammation at the fetal maternal interface on both term and preterm labor. Inflammophilic oral bacteria, such as Porphyromonas gingivalis, as well as urogenital microorganisms (UGM) could translocate to the placenta and activate immune mechanisms in decidual tissue that is associated with adverse pregnancy outcomes (APO). This study establishes the associations between the presence of microbes in the placenta and placental cytokine patterns in women who presented APO, e.g., low birth weight (LBW), preterm premature rupture of membranes (PPROM), preterm birth (PTB) and other clinical signs related to Chorioamnionitis (CA). A total of 40 pregnant women were included in the study and divided into five groups according to placental infection (PI) and APO, as follows: (1) women without PI and without APO (n = 17), (2) women with P. gingivalis-related PI and APO (n = 5), (3) women with P. gingivalis-related PI and without APO (n = 4), (4) women with PI related to UGM and APO (n = 5) and (5) women without PI with APO (n = 9). Obstetric, clinical periodontal status evaluation, and subgingival plaque sampling were performed at the time of delivery. Placental levels of interleukin IL-1β, IL-6, IL-10, IL-15, IL-17A, IL-17F, IL-21, IL-12p70, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 α (MCP-1α), granzyme B, and interferon-γ (IFN-γ) were determined using a multiplex flow cytometry assay. All patients showed a predominant Th-1 cytokine profile related to labor, characterized by IFN-γ overexpression. The analysis by groups suggests that Th-1 profile was trending to maintain cytotoxic cell activity by the expression of IL-15 and granzyme B, except for the group with P. gingivalis-related PI and APO, which exhibited a reduction of IL-10 and IL-17F cytokines (p < 0.05) and a Th-1 profile favoring macrophage activation by MCP-1 production (p < 0.05). This study confirms a pro-inflammatory pattern associated with labor, characterized by a Th-1 profile and the activity of cytotoxic cells, which is enhanced by PI with UGM. However, PI associated with P. gingivalis suggests a switch where the Th-1 profile favors an inflammatory response mediated by MCP-1 and macrophage activity as a mechanistic explanation of its possible relationship with adverse outcomes in pregnancy.

Changes in the systemic inflammatory response in women in the third trimester of pregnancy complicated by exacerbation of cytomegalovirus infection

Aim . To study the change in the systemic inflammatory response in women in the third trimester of pregnancy complicated by exacerbation of cytomegalovirus infection (CMVI). Materials and methods. The study involved 120 women with a physiological course of gestation and with a pregnancy complicated by CMVI. The first group was represented by 30 seronegative women at 31-34 weeks of gestation, the second – by 30 pregnant women with a latent course of CMVI and placental insufficiency, the third – 30 women with exacerbation of CMVI and placental insufficiency; and the fourth – 30 patients with exacerbation of CMVI, initiating the development of placental insufficiency and threatened miscarriage. Results. In the blood serum of women in the first group, the TNF-α content was 14.7 (12.1-32.0) pg/mL, IFN-γ – 128.7 (117.0-172.5) pg/mL, IL-1β – 20.3 (13.8-35.3) pg/mL, IL-6 – 2,57 (2,10-2,73) pg/mL, IL-4 – 37,8 (30,0- 55,4) pg/mL and IL-2 – 34,3 (29,4-41,3) pg/mL. The patients of the second group, in comparison with the first one, were diagnosed with an increase in the median TNF-α to 29.5 (14.4-43.1) pg/mL (p=0.0168) and IL-2 – 40.7 (33.2-47.9) pg/mL (p=0.0169) against the background of the absence of significant differences in the concentration of IFN-γ, IL-1β, IL-6 and IL-4. In the third group, compared with the second one, the concentration of TNF-α increased by 2.74 times (p=0.000001), IFN-γ – by 1.69 times (p=0.000001), IL-1β – by 3.16 times (p=0.000001), IL-6 – 2.17 times (p=0.000001), IL-2 – 2.2 times (p=0.000001) and there were no differences in the concentration of IL-4 (p=0.994). In the fourth group, compared with the third one, an increase in TNF-α level was diagnosed by 1.03 times (p=0.028), IFN-γ – by 1.18 times (p=0.017), IL-1β – by 1.64 times (p=0.000001), IL-6 – by 1.49 times (p=0.0035), IL-2 – by 1.32 times (p=0.000001) against the background of a drop in IL-4 level by 1.52 times (p=0.00031). Conclusion. Increase in serum concentration of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-2) against the background of a decrease in the level of anti-inflammatory cytokine (IL-4) in women with exacerbation of CMVI in the third trimester of gestation, complicated by placental insufficiency, plays an important role in the pathogenesis of threatened preterm labor.

Cytokine responses across submaximal exercise intensities in women with major depressive disorder

BackgroundMajor depressive disorder (MDD) is associated with chronic inflammation. Exercise training can treat depression in adults with MDD, potentially through reducing inflammatory activity. This improvement may occur through adaptations to repeated acute inflammatory responses. Cytokine responses to acute steady-state exercise of varying intensities were determined in women with different levels of depression. MethodsThis analysis included 19 women with MDD who each participated in four sessions consisting of 30 ​min of quiet rest, light, moderate, or hard intensity exercise. Blood samples were collected pre- and within 10 ​min post-session. Changes in the levels of IL-6, IL-8, IL-10, and TNF were evaluated in each session. ResultsSerum concentrations of IL-6, IL-8 and TNF were all significantly elevated following vigorous exercise (i.e., hard) compared to the quiet rest session. No changes in cytokine levels occurred after light and moderate exercise. Depression severity did not appear to influence the acute inflammatory response to exercise. LimitationsThe sample size was small, all female, and from a secondary data analysis, which limits the generalizability of the findings. ConclusionsRepeat, acute increases in inflammatory activity following hard exercise sessions may prompt adaptations and lead to reductions in chronic inflammation over time. This dose-response study identified an exercise intensity threshold to induce acute inflammatory responses in women with MDD.

Serum levels of tumor necrosis factor- α and interleukin -10, and their clinical correlates in women with pre-eclampsia/eclampsia in Ahmadu Bello University Teaching Hospital

Background: Pre-eclampsia is a pregnancy-specific disorder characterized by the onset of hypertension and proteinuria after the 20th week of gestation. It is characterized by an exaggerated maternal inflammatory response with a preponderance of cell-mediated immune response. Tumor necrosis factor-alpha (TNF-α) is a pro-inflammatory cytokine that induces apoptosis and restrains differentiation. Defective trophoblastic invasion is now identified as the key etiology of pre-eclampsia. The objective of this study was to determine the serum levels TNF-α and interleukin 10 (IL-10) in women with pre-eclampsia/eclampsia and the relationship between these cytokines and the severity of the disease. Patients and Method: This was a case-control study carried out in Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Forty-eight patients with a diagnosis of pre-eclampsia/eclampsia were recruited as cases. The diagnosis was according to the International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria. For each case, a healthy pregnant control was selected, after matching for age, gestational age, and parity. Blood samples were taken and assayed for TNF-α and IL 10 using enzyme-linked immunosorbent assay. Data were analyzed using SPSS v 20. A P value Results: The prevalence of pre-eclampsia/eclampsia in ABUTH Zaria is 5.1%. Nulliparous women constituted 65.9% of the patients. Thirty-five percent of the women were between 20 and 24 years of age. The mean serum levels of TNF-α in women with pre-eclampsia/ eclampsia and controls were 294.8 ± 146 pg/mL and 176 ± 35.5 pg/mL, respectively. The mean serum levels of IL-10 in patients and controls with pre-eclampsia were 13.9 ± 5.7 pg/mL and 33.0 ± 11.0 pg/mL, respectively. The levels of TNF-α correlated positively with the severity of the disease. The serum levels of IL-10 did not correlate with disease severity. Conclusion: The prevalence of pre-eclampsia/eclampsia is high in ABUTH. The disease is characterized by an exaggerated inflammatory response in women in Zaria. Use of anti- TNF-α drugs may possibly have a role in the prevention of pre-eclampsia.

The earlier the gestational age, the greater the intensity of the intra-amniotic inflammatory response in women with preterm premature rupture of membranes and amniotic fluid infection by Ureaplasma species.

Objectives To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0-33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0-36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp.

Clinical chorioamnionitis at term IX: in vivo evidence of intra-amniotic inflammasome activation.

Background The inflammasome has been implicated in the mechanisms that lead to spontaneous labor at term. However, whether the inflammasome is activated in the amniotic cavity of women with clinical chorioamnionitis at term is unknown. Herein, by measuring extracellular ASC [apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (CARD)], we investigated whether there is in vivo inflammasome activation in amniotic fluid of patients with clinical chorioamnionitis at term with sterile intra-amniotic inflammation and in those with intra-amniotic infection. Methods This was a retrospective cross-sectional study that included amniotic fluid samples collected from 76 women who delivered after spontaneous term labor with diagnosed clinical chorioamnionitis. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin (IL)-6 concentration ≥2.6 ng/mL, and intra-amniotic infection was diagnosed by the presence of microbial invasion of the amniotic cavity (MIAC) accompanied by intra-amniotic inflammation. Patients were classified into the following groups: (1) women without intra-amniotic inflammation or infection (n=16); (2) women with MIAC but without intra-amniotic inflammation (n=5); (3) women with sterile intra-amniotic inflammation (n=15); and (4) women with intra-amniotic infection (n=40). As a readout of in vivo inflammasome activation, extracellular ASC was measured in amniotic fluid by enzyme-linked immunosorbent assay. Acute inflammatory responses in the amniotic fluid and placenta were also evaluated. Results In clinical chorioamnionitis at term: (1) amniotic fluid concentrations of ASC (extracellular ASC is indicative of in vivo inflammasome activation) and IL-6 were greater in women with intra-amniotic infection than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (2) amniotic fluid concentrations of ASC and IL-6 were also higher in women with sterile intra-amniotic inflammation than in those without intra-amniotic inflammation, regardless of the presence of MIAC; (3) amniotic fluid concentrations of IL-6, but not ASC, were more elevated in women with intra-amniotic infection than in those with sterile intra-amniotic inflammation; (4) a positive and significant correlation was observed between amniotic fluid concentrations of ASC and IL-6; (5) no differences were observed in amniotic fluid ASC and IL-6 concentrations between women with and without MIAC in the absence of intra-amniotic inflammation; (6) women with intra-amniotic infection had elevated white blood cell counts and reduced glucose levels in amniotic fluid compared to the other three study groups; and (7) women with intra-amniotic infection presented higher frequencies of acute maternal and fetal inflammatory responses in the placenta than those with sterile intra-amniotic inflammation. Conclusion The intra-amniotic inflammatory response, either induced by alarmins or microbes, is characterized by the activation of the inflammasome - as evidenced by elevated amniotic fluid concentrations of extracellular ASC - in women with clinical chorioamnionitis at term. These findings provide insight into the intra-amniotic inflammatory response in women with clinical chorioamnionitis at term.

Amniotic fluid cell-free DNA in preterm prelabor rupture of membranes.

We evaluated the levels of cell-free nuclear DNA (nDNA) and cell-free mitochondrial DNA (mtDNA) in the amniotic fluid supernatant from pregnancies complicated by preterm prelabor rupture of membranes (PPROM) based on evidence of microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI). A total of 155 women with PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. The levels of cell-free nDNA and mtDNA in the amniotic fluid supernatant were assessed and quantified by real-time polymerase chain reaction. The levels of cell-free nDNA and mtDNA were higher in women with MIAC and IAI than in women without these conditions (nDNA: with MIAC: median 3.9×104 genome equivalent [GE]/mL vs without MIAC: median 1.2×104 GE/mL, with IAI: median: 5.3×104 GE/mL vs without IAI: median 1.2×104 GE/mL; mtDNA: with MIAC: median 9.2×105 GE/mL vs without MIAC: median 2.5×105 GE/mL, with IAI: median 1.1×106 GE/mL vs without IAI: median 2.5×105 ; all P values≤0.01). Women with the microbial-associated IAI showed the highest levels of cell-free nDNA and mtDNA. Cell-free nDNA and mtDNA are constituents of the amniotic fluid supernatant from PPROM pregnancies. Both cell-free nDNA and mtDNA are involved in the intra-amniotic inflammatory response in women with PPROM.

The Role of Polymorphonuclear Leukocyte Counts from Urethra, Cervix, and Vaginal Wet Mount in Diagnosis of Nongonococcal Lower Genital Tract Infection.

Objective The aim of this study was to evaluate whether the polymorphonuclear leukocyte (PMNL) inflammatory response in women with nongonococcal lower genital tract infection (LGTI) can be used to optimize criteria for syndromic treatment. Methods A cross-sectional study of 375 women attending the STI clinic in Oslo. Urethral, cervical, and vaginal specimens underwent microscopy for PMNLs. Chlamydia trachomatis (Ct) and other STIs were detected in the cervical/vaginal swabs and urine, using nucleic acid amplification test (NAAT). After excluding vulvovaginal candidiasis, genital herpes, and trichomoniasis, we correlated clinical and microscopic signs of inflammation with positive NAAT for Ct, mycoplasma genitalium (Mg), and Ureaplasma urealyticum (Uu) in a subgroup of 293 women. Results To predict a positive Ct, the combination of high cut-off urethritis (≥10 PMNLs/HPF) and microscopic cervicitis had a high specificity of 0.93, a PPV of 0.37, and a sensitivity of 0.35. LGTI criteria had low predicting values for Mg and Uu. Conclusion Including microscopic criteria for the diagnosis of LGTI gives better indication for presumptive antibiotic treatment than anamnestic and clinical diagnosis alone.

Митохондриальные белки микровезикул плазмы периферической крови как триггеры асептических воспалительных реакций у женщин с угрожающим и привычным выкидышем и физиологическим течением беременности

Митохондриальные белки микровезикул плазмы периферической крови как триггеры асептических воспалительных реакций у женщин с угрожающим и привычным выкидышем и физиологическим течением беременности

Correction: Systemic and Local Inflammatory Response in Women with Preterm Prelabor Rupture of Membranes

[This corrects the article DOI: 10.1371/journal.pone.0085277.].

Levels of multiple proteins in gingival crevicular fluid and intra-amniotic complications in women with preterm prelabor rupture of membranes

Objective: The primary aim of this study was to identify the association between the local inflammatory response in gingival crevicular fluid measured by the levels of multiple proteins and maternal and intra-amniotic inflammatory responses measured by maternal serum C-reactive protein (CRP) and amniotic fluid interleukin (IL)-6 concentrations, respectively, in women with preterm prelabor rupture of membranes (PPROM).Methods: A prospective study was performed in which 78 women with singleton pregnancies complicated by PPROM between 24 + 0 and 36 + 6 weeks of gestation were included. Transabdominal amniocenteses were performed at the time of admission. A bedside assessment of amniotic fluid IL-6 was performed. Maternal serum CRP concentration was also measured at the time of admission. Gingival crevicular fluid was collected from the pocket of the selected tooth (the tooth with the deepest pocket) using standard sterile paper strips within 72 h after admission. Twenty-six proteins in the gingival crevicular fluid were assessed by multiplex the Meso-Scale technology.Results: No correlations between the levels of proteins in the gingival crevicular fluid and maternal serum CRP and amniotic fluid IL-6 concentrations were found, except for a weak positive correlation between granulocyte macrophage colony-stimulating factor and CRP.Conclusions: The local inflammatory response in the gingival crevicular fluid is not related to the maternal and intra-amniotic inflammatory responses in women with PPROM.

Abstract P314: Higher C-Reactive Protein Levels Among Women with a History of Hypertensive Disorders of Pregnancy

Introduction: Women with a history of pregnancy complications, including hypertensive disorders of pregnancy (HDP: preeclampsia and gestational hypertension) and preterm delivery (&lt;37 weeks), have an increased risk of cardiovascular disease (CVD). There is limited knowledge of the pathway linking pregnancy outcomes and CVD, but chronic inflammation may play a role. Methods: We selected parous women from the Nurses’ Health Study II who had the inflammatory biomarkers C-reactive protein (CRP; n=2,987) or interleukin (IL)-6 (n=2,916) assessed in stored blood samples provided after pregnancy, between 1996 and 1999. Women were selected from previous nested case-control biomarker studies. Robust linear regression models were used to separately evaluate the mean differences in CRP and IL-6 and 95% confidence intervals (CIs) associated with a history of HDP compared to no such history and with a history of preterm delivery compared to no such history. Models were adjusted for age at blood draw, pre-pregnancy body mass index and smoking, and variables related to lab selection. Results: Ten percent (285 of 2,987) of women had a history of HDP, while 12% (358 of 2,987) had at least one preterm delivery prior to blood draw. Median time from first pregnancy to blood draw was 17 years (range: 1-37 years). Mean CRP levels were 2.00 mg/L and 1.57 mg/L, while mean IL-6 levels were 1.56 pg/mL and 1.42 pg/mL in women with and without a history of HDP, respectively. In women with and without preterm delivery, mean CRP levels were 1.54 mg/L and 1.62 mg/L and mean IL-6 levels were 1.39 pg/mL and 1.44 pg/mL, respectively. Plasma levels of CRP were 0.36 mg/L (95% CI: 0.12, 0.60) higher, on average, in women with a history of HDP compared to those with all normotensive pregnancies. Plasma IL-6 levels were not significantly higher among women with a history HDP (0.06 pg/mL, 95% CI: -0.16, 0.27). There were no significant differences in CRP (-0.11 mg/L, 95% CI: -0.30, 0.07) or IL-6 (-0.08 pg/mL, 95% CI: -0.25, 0.10) levels in women with a history of preterm delivery. Conclusion: CRP was elevated in women with a history of HDP in the decades following pregnancy, suggesting a potential inflammatory response. An altered inflammatory profile was not present in women with a history of preterm delivery. Further investigation is needed to confirm these inflammatory responses in women with a history of pregnancy complications and to evaluate the utility of CRP as a potential risk marker in CVD screening.