Cytokines In Pregnant Women Research Articles

Multi-omics analysis reveals the associations between altered gut microbiota, metabolites, and cytokines during pregnancy.

For embryo implantation and fetal development, the maternal immune system undergoes dramatic changes. The mechanisms involved in inducing alterations of maternal immunity have not been fully clarified. Gut microbiome and metabolites were thought to influence the host immune response. During normal pregnancy, notable changes occur in the gut microbiota and metabolites. However, the relationship of these alterations to immune function during pregnancy remains unclear. In this study, we examined gut microbiota, fecal metabolites, plasma metabolites, and cytokines in pregnant women and non-pregnant women. Our findings revealed that, in comparison to non-pregnant women, pregnant women exhibit a significant increase in the relative abundance of Actinobacteriota and notable differences in metabolic pathways related to bile acid secretion. Furthermore, there was a marked reduction in pro-inflammatory cytokines levels in pregnant women. Correlation analyses indicated that these alterations in cytokines may be linked to specific gut bacteria and metabolites. Bacteria within the same microbial modules exhibited consistent effects on cytokines, suggesting that gut bacteria may function as functional groups. Mediation analysis further identified that certain bacteria might influence cytokines through metabolites, such as bile acids and arachidonic acid. Our findings propose potential biological connections between bacteria, metabolites, and immunity, which require further validation in future studies.IMPORTANCEA great number of studies have focused on diseases induced by intestinal microecological disorders and immune imbalances. However, the understanding of how intestinal microbiota interacts with immunity during normal pregnancy, which is fundamental to studying pathological pregnancies related to intestinal microbiota disturbances, has not been well elucidated. Our study employed multi-omics analysis to discover that changes in gut microbiota and metabolites during pregnancy can impact immune function. In addition, we identified several metabolites that may mediate the effect of gut microbes on plasma cytokines. Our study offered new insights into our understanding of the connections between the gut microbiome, metabolome, and the immune system during pregnancy.

Expression of miRNAs and proinflammatory cytokines in pregnant women with gestational diabetes mellitus

Altered microRNAs (miRNAs11miRNA – microRNA) and cytokines expression levels are associated with several pregnancy-induced complications. We evaluated the profile of circulating miRNAs (miR-17, miR-29a and miR-181a) and proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-17) in women with gestational diabetes mellitus (GDM22GDM – gestational diabetes mellitus), as well as their potential use as GDM biomarkers. The case-control study included 65 pregnant women divided into 2 groups - GDM and control. Expression levels of miRNAs in plasma samples and cytokines mRNA isolated from peripheral blood buffy coat were analyzed by quantitative real-time PCR (qPCR33qPCR - quantitative real-time PCR). Significant miR-29a downregulation was found in GDM compared to the control group, and was even more significant after adjustments for covariates. miR-17 and miR-181a expression levels did not differ between the examined groups. Expression levels of IL-1β were significantly higher in GDM group compared to controls, while TNF-α, IL-6 and IL-17 did not show significant changes in expression between the two groups. As jugded from the ROC curve analysis, miR-29a and IL-1β had a significant capacity to discriminate between CG and GDM. Additionally, a positive correlation was established between IL-1β and TNF-α in the GDM group. GDM appeared to be associated with altered levels of miR-29a and IL-1β making them markers of this condition.

Cytokine responses to SARS-COV2 infection in mother-infant dyads: a systematic review and meta-analysis.

The COVID-19 pandemic has affected a significant number of pregnant women worldwide, but studies on immune responses have presented conflicting results. This study aims to systematically review cytokine profiles in pregnant women with SARS-CoV-2 infection and their infants to evaluate immune responses and potential transplacental transfer of cytokines. A comprehensive search of 4 databases was conducted to identify relevant studies. Inclusion criteria included studies measuring individual cytokines in pregnant women and/or their neonates. Studies were evaluated for quality, and data were extracted for analysis. Meta-analyses were performed using the random-effects model. Seventeen studies met the inclusion criteria, including data from 748 pregnant women and 287 infants. More than three of these studies evaluated data of 20 cytokines in maternal serum, and data of 10 cytokines was available from cord blood samples. Only the serum level of CXCL10 was significantly up-regulated in SARS-CoV-2 positive pregnant women (n = 339) compared to SARS-CoV-2 negative pregnant women (n = 409). Subset analysis of maternal samples (n = 183) collected during the acute phase of COVID-19 infection showed elevated CXCL10 and IFN-γ. No significant differences in cytokine levels were found between cord blood samples collected from infants born to mothers with (n = 97) and without (n = 190) COVID-19 during gestation. Subset analysis of cord blood samples collected during the acute phase of maternal infection was limited by insufficient data. The heterogeneity among the studies was substantial. The findings suggest that maternal cytokines responses to SARS-CoV-2 infection during pregnancy are not significantly dysregulated, except for CXCL10 and IFN-γ during the acute phase of illness. No evidence of increased cytokine levels in cord blood samples was observed, although this could be impacted by the time period between initial maternal infection and cord blood collection. These results provide some reassurance to parents and healthcare providers but should be interpreted cautiously due to study variations and limitations.

Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women.

The prevalence of obesity among women of child-bearing age has contributed to an increased risk of pregnancy complications with a disproportional impact on women of lower socioeconomic status and among certain racial groups. In particular, socio-demographic and historical factors have resulted in higher rates of premature births and small-for-gestational age infants among Black women, which may be associated with placental function during pregnancy. The current study investigated the influence of maternal pre-pregnancy adiposity and race on the associations between inflammatory proteins, placental growth hormone (PGH), and infant birthweight. This information was collected for a subsample of 109 participants (Black, n = 39 vs. White, n = 70) from the Brain and Early Experiences (BEE) study. Serum samples were acquired late in the second trimester to assess PGH levels, C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin-1 receptor antagonist (IL-1Ra). Participant questionnaire responses provided information on pre-pregnancy BMI, health, race, educational attainment, and infant birthweight. Bivariate correlations and multiple linear regression models were utilized to evaluate associations by race between preconception adiposity, inflammatory markers and PGH. After controlling for covariates including maternal age and education, gestational age, and fetal sex, regression models indicated that pre-pregnancy BMI was negatively associated with PGH (β=-0.42, p<0.05) and IL-8 was positively associated with PGH (β=0.35, p<0.05) among the Black mothers only; neither were significantly associated with PGH in the White mothers. When extending models to birth outcomes, BMI was positively associated with birthweight corrected for gestational age (BWz) (β=0.24, p<0.05) and educational attainment was negatively associated with BWz (β=0.28, p<0.05) for infants of White women. In contrast, neither variable was predictive of BWz for infants of Black mothers. Future work is needed to investigate racial differences in the association between adiposity and placental functioning, which are likely to contribute to differential effects on pregnancy outcomes and fetal growth.

Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women

Racial differences in the associations between adiposity, placental growth hormone and inflammatory cytokines in pregnant women

Benefits of Hydroxychloroquine Combined with Low-Dose Aspirin on Pregnancy Outcomes and Serum Cytokines in Pregnant Women with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease, with hydroxychloroquine being the main therapeutic agent for the treatment of SLE. This research explored the effects of hydroxychloroquine combined with low-dose aspirin on maternal and infant outcomes and cytokines of pregnant women with SLE. Ninety pregnant women with SLE were divided into the hydroxychloroquine (HCQ) group (45 cases) and the hydroxychloroquine combined with low-dose aspirin (HCQASP) group (45 cases) by random number table. Patients in the HCQ group were treated with oral administration of hydroxychloroquine, while patients in the HCQASP group were treated with low-dose aspirin based on oral administration of hydroxychloroquine. Pregnancy outcomes, fetal outcomes, and cytokine levels were statistically analyzed. The HCQASP group had a significantly higher proportion of full-term pregnancies and a significantly lower proportion of hypertension, prematurity, and pregnancy loss than the HCQ group. Neonates in the HCQASP group also had significantly higher birth weights and Apgar scores and a significantly lower proportion of neonatal asphyxia than the HCQ group. After treatment, the HCQASP group had significantly higher interleukin (IL-2) and interferon (IFN)-γ levels and significantly lower IL-4 and IL-10 levels than the HCQ group. Hydroxychloroquine combined with low-dose aspirin can effectively improve the pregnancy outcomes of pregnant women with SLE by affecting the levels of T helper (Th)2 and Th1 cytokines.

Effects of Different Progesterone Doses on the Concentrations of Proinflammatory and Anti-inflammatory Cytokines in Pregnant Women With Threatened Abortion.

Background and objectiveThis study aimed to investigate how different doses of progesterone influence the concentrations of interleukin-6 (IL-6) and tumor necrotizing factor-alpha (TNF-α), which are proinflammatory cytokines, as well as that of IL-10, which is an anti-inflammatory cytokine, in pregnant women with threatened abortion.Materials and methodsThis is a prospective, single-center, randomized controlled trial conducted with 221 patients with a threatened abortion diagnosis. Group 1 consisted of IL-6, IL-10, and TNF-α values in pre-treatment blood samples from 221 patients diagnosed with imminent abortion. Group 2 included 81 patients who received natural oral 100 mg micronized progesterone MP twice a day for two weeks. Group 3 included 83 patients who were administered oral 200 mg of natural micronized progesterone MP twice a day for two weeks. Group 4 included 57 patients who received oral 200 mg of natural micronized progesterone MP twice a day for two weeks, and one depot progesterone was added to the treatment by administering it at a dosage of 500 mg/day intramuscularly.ResultsIL-6 values between groups were lower in group 4 compared to group 3 (p=0.007). When IL-10 values were compared between the groups, the IL-10 ratio was highest in group 4 and lowest in group 2 (p<0.001, p=0.003, p<0.001). When the TNF-α values between the groups were compared, the value in group 4 was decreased compared to groups 1 and 2 (p=0.031, p<0.001). In the logistic regression analysis, the IL-6 value above 12.01 increased the abortion imminens rate 1.01 times, and a TNF-α value above 11.04 increased the abortion imminens rate 1.21 times.ConclusionProgesterone used to treat imminent abortion reduces the levels of proinflammatory cytokines, such as IL-6 and TNF-α, while increasing those of anti-inflammatory cytokine IL-10 in proportion to the dose administered. Progesterone can prevent imminent abortion by generating an anti-inflammatory environment.

Levels of some cytokines in pregnant women with covid-19 infection

The current work was objective to estimate the levels of some cytokines in pregnant women with COVID-19 infection. A total of 58 blood samples were obtained from infected pregnant women with COVID-19 and 30 healthy pregnant women (age range: 18–40 years). The blood samples collected (at a period June 2020 to January, 2021) from Al Shifa Medical Center, Azadi Teaching Hospital, Kirkuk, Iraq. The findings of current work showed that the levels of D-dimer in infected pregnant women significant elevated compared with healthy pregnant women. On the other hand, the findings showed that the levels of IL-6 and IL-10 in infected pregnant women significant elevated compared with healthy pregnant women. Therefore, it is concluded from the current work that infection with the COVID-19 cause higher levels of cytokines that have been studied in infected pregnant women compared to healthy pregnant women. © 2021, Dr. Yashwant Research Labs Pvt. Ltd.. All rights reserved.

Y-012. Metformin changes serum cytokines in pregnant women with polycystic ovary syndrome

Determine if perioperative hypotension, a modifiable risk factor, is associated with increased postoperative healthcare resource utilization (HRU).Retrospective cohort study.Multicenter using the Optum® electronic health record database.Patients discharged to the ward after non-cardiac, non-obstetric surgeries between January 1, 2008 and December 31, 2017 with six months of data, before and after the surgical visit.Perioperative hypotension, a binary variable (presence/absence) at an absolute MAP of ≤65-mmHg, measured during surgery and within 48-h after, to dichotomize patients with greater versus lesser hypotensive exposures.Short-term HRU defined by postoperative length-of-stay (LOS), discharge to a care facility, and 30-day readmission following surgery discharge. Mid-term HRU (within 6 months post-discharge) quantified via number of outpatient and emergency department (ED) visits, and readmission LOS.42,800 distinct patients met study criteria and 37.5% experienced perioperative hypotension. After adjusting for study covariates including patient demographics and comorbidities, patients with perioperative hypotension had: longer LOS (4.01 vs. 3.83 days; LOS ratio, 1.05; 95% CI, 1.04–1.06), higher odds of discharge to a care facility (OR, 1.18; 95% CI, 1.12–1.24; observed rate 22.1% vs. 18.1%) and of 30-day readmission (OR, 1.22; 95% CI, 1.11–1.33; observed rate 6.2% vs. 5.0%) as compared to the non-hypotensive population (all outcomes, p < 0.001). During 6-month follow-up, patients with perioperative hypotension showed significantly greater HRU regarding number of ED visits (0.34 vs. 0.31 visits; visit ratio, 1.10; 95% CI, 1.05–1.15) and readmission LOS (1.06 vs. 0.92 days; LOS ratio, 1.15; 95% CI, 1.07–1.24) but not outpatient visits (10.47 vs. 10.82; visit ratio, 0.97; 95% CI, 0.95–0.99) compared to those without hypotension. There was no difference in HRU during the 6-month period before qualifying surgery.We report a significant association of perioperative hypotension with an increase in HRU, including additional LOS and readmissions, both important contributors to overall medical costs.

RELAXIN AND IMMUNE FACTORS AS PREDICTORS OF BIOLOGICAL PREPARATION FOR LABOUR

Introduction. Biological preparedness for childbirth plays an important role in ensuring the normal course of spontaneous labour, as well as determining the criteria for preinduction and induction of labour with obstetrics pathologies. Recent studies have shown that labour involves a complex interaction between maternal and fetal factors that contribute to cervical maturation and myometrial contraction. In its turn it prompts the search for predictors that allow early identification of pathologies and improve the prognosis. The Relaxin hormone may function as one of the aforementioned predictors due to the emerging evidence for its involvement in the pathogenesis of abortion. Studies show that Relaxin plays a key role in the adaptation of a female 51 body by targeting the cervix among other organs. Relaxin acts on the cervix by degrading extracellular matrix components through activation of proteolytic enzymes, known as matrix metalloproteinases (MMPs). Remodeling of the cervix is a combination of endocrine and immune interactions. One of the hallmarks of cervix remodeling is infiltration of leukocytes prior to labour. These tissue granulocytes become the source of proinflammatory cytokines that upregulate MMPs. Relaxin controls the local inflammatory response by modulating matrix metalloproteinases. Thus, understanding the regulatory role of Relaxin in systemic production of cytokines and its effect on neutrophils at different stages of cervical maturation is of great interest. Aim: characterise the interplay between Relaxin, cytokines and their joint role in regulation of proteolytic enzymes to establish new criteria for prognosis of cervical maturation. Materials and methods. 69 pregnant women of gestational age 38-40 weeks were examined. The examined women were divided into 3 clinical groups, depending on the degree of cervix maturity at the time of hospitalisation. The degree of cervix maturity was assessed by the EH Bishop scale. Group I consisted of 23 patients with a mature cervix (9-13 points), group II included 21 pregnant women with an immature cervix (6-8 points), group III contained 25 pregnant women with a completely immature cervix (0-5 points). The control group consisted of 15 women of gestational age 35-36 weeks, who were pregnant for the first time. Women of the control group were examined prior to the start of physiological processes of remodeling of cervical tissues before labour and displayed no signs of premature labour. Control group was compared to women from the I, II and III groups by disease history and somatic data. All pregnant women underwent standardized clinical examination and immunological testing. Serum concentration of cytokines IL-6 and TNF-α, MMP-1 and MMP-9, and Relaxin levels were determined by enzyme-linked immunosorbent assay using commercial kits. Statistical analysis of the results was performed using the program "STATISTICA-6". Statistical significance was calculated by Student's t-test. Spearman's rank correlation coefficient was determined between the obtained parameters. The differences were considered accurate with a significance level of p&lt;0.05. Results. The average age of the examined pregnant women was 25 years 7 months (18-33). All patients of the examined groups could be compared to each other by their age, genital features and menstrual function (p ≤ 0.05). The study has shown that the lowest serum concentration of Relaxin was found in women with immature or completely immature cervix, which accounted to 189.7±34.6 pg / ml and 208, 9±27.6 pg / ml, respectively. This suggests that serum concentration of Relaxin could serve as a possible predictor of biological readiness of the body for labour. Furthermore, serum Relaxin concentration can serve as a prognostic marker of the effectiveness of induction and preinduction of labour. The data presented shows that women with mature cervix display maximum levels of matrix metalloproteinases MMP9 and MMP-1. Specifically, the concentration was 1.8 times higher than in the group of women with immature cervix. Thus, maturation of the cervix uterus involves a significant increase in the concentration of matrix metalloproteinases by peripheral neutrophils with a gradual increase in their proteolytic activity. Our study showed that high serum concentrations of the proinflammatory cytokines in pregnant women with a mature cervix before labour were higher compared to women with an immature or completely immature cervix. The interplay between proinflammatory cytokines and other modulators presented here during the preparation of the body for labour was evident from the observed correlation. We observed a strong correlation between the level of Relaxin and matrix metalloproteinases (r = 0, 78), as well as positive correlation between their content and the cytokines of interest. Conclusion. The study allowed to identify the most prognostically significant molecular predictors that characterize the body's preparation for labour, which include the "birth hormone" Relaxin. Furthermore, our analysis implicates immune mechanisms in regulating cervical maturation before labour.

Maternal Serum Levels of Alpha Tumour Necrotic Factor, Interleukin 10, Interleukin 6 and Interleukin 4 in Malaria Infected Pregnant Women Based on Their Gestational Age in Southeast, Nigeria

Malaria has been reported as a condition caused by infestation with Plasmodium parasite species, is a major public health problem globally especially in developing countries like Nigeria. This study was carried out in Federal Medical Centre Umuahia in Abia State, Nigeria. A study was done to determine the maternal serumlevels of alpha tumour necrotic factor, interleukin 10, interleukin 6and interleukin 4 in malaria infected pregnant women based on their gestational age in Southeast, Nigeria. A total of 150 subjects between the ages of 18-45 years were recruited for the study comprising of fifty (50) subjects each of the 3 trimesters. Commercial ELISA Kit by MELSIN Medical Co Limited was used to measure all the cytokines. The results of Table 1 showed no significant difference of TNF-α (p=0.346), IL-10 (p=0.059), IL-6 (p=0.811) and IL-4 (p=0.257) of malaria infected pregnant women at first trimester and second trimester respectively. The results of Table 2 showed no significant difference of TNF-α (p=0.642), IL-10 (p=0.678), IL-6 (p=0.551) and IL-4 (p=0.280) of malaria infected pregnant women at first trimester and third trimester respectively. The results of Table 2 showed no significant difference of TNF-α (p=0.062), IL-10 (p=0.016), IL-6 (p=0.352) and IL-4 (p=0.914) of malaria infected pregnant women at first trimester and third trimester respectively. The study showed no changes in the cytokines studied among the malaria infected pregnant women based on gestational ages except when IL-10 was compared between the subjects on second trimester and third trimester. This study shows that malaria infection does not changes these cytokines in pregnant women based on gestational ages except the il-10 when compared at second trimester and third trimester but changes when compared at other trimesters.

Role of cytokines in pregnant women with chronic iron deficiency anemia in preeclampsia pathogenesis

The frequency of development of hypertensive states in IDA reaches 32-45%. The pathogenesis of the combined complications of pregnancy with anemia and preeclampsia, including immunological aspects has been little studied. Purpose: to clarify the role of violations general and local cytokine status in pregnant women with anemia in the genesis of preeclampsia and justify the need to include immuno suppressants for the prevention and treatment of preeclampsia. Materials and methods: In 96 pregnant women with iron deficiency anemia (IDA) and preeclampsia in the third trimester of gestation the cytokine status of IL-1β, IL-6, IL-8, TNFα and lactoferrin in the serum of peripheral blood and in extracts of the placenta decidual tissue was examined by ELISA. Pregnant women were divided into 4 groups: 24-with mild anemia, 18-with moderate anemia, 26-with preeclampsia and with mild anemia and 28 pregnant women with preeclampsia and with moderate anemia. Results: It has been established that preeclampsia on the background of IDA is accompanied by a significant increase in the level of pro-inflammatory cytokines (p&lt;0,05) and the acute phase protein lactoferrin (p&lt;0,05) on the systemic and to a greater extent on the local level in the development of preeclampsia on the background of anemia of moderate severity (p&lt;0,05). Discussion: The data obtained confirm the involvement of the immune system in the pathogenesis of preeclampsia, one of the trigger mechanisms of which is the immune imbalance in iron deficiency anemia. A pathogenetic rationale for the use of immunosuppressive therapy for combined pathology is given. Conclusion: The use of placental hormone - progesterone as an immunosuppressive drug in terms of substantiating new immunotherapy strategies for the prevention of preeclampsia is a topical trend in obstetric practice.

Cytokines Level (Il8 and Il17) in Pregnant Women with Toxoplasmosis in Khartoum State

Toxoplasmosis is one of the most important zoonotic diseases worldwide caused by Toxoplasma gondii that leads to abortion or hydrocephalus during pregnancy. It’s a comparative cross-sectional one designed to assess immunoglobulins and cytokines in pregnant women. A total of 300 venous blood samples were collected from each pregnant woman and centrifuged to obtain serum. Patient’s information was recorded in a questionnaire previously designed for the purpose of analysis. In addition, 40 uninfected women were enrolled in the study as control group to assess the level of IL8 and IL17 cytokines. The overall seropositive rate of Toxoplasma gondii infection was 22.6%. Within the positive cases of study population, only 16 and 13 showed positive results of IL8, IL17 respectively. The results showed highly significant increase in the mean serum level of IL8 (210.25pg/ml) and IL17 (203.15 pg/ml) when compared to the control group who showed 68.9 pg/ml and 54.8 pg/ml respectively. The serum level of proinflammatory cytokines investigated in this study seems to be increased in patients with serological evidence of Toxoplasma gondii infection. Our study concludes that IL-17 and IL-8 involved in the induction of inflammation and toxoplasmosis disease.

Melatonin decreases and cytokines increase in women with placental insufficiency

Purpose: To investigate the levels of melatonin, proinflammatory and anti-inflammatory cytokines in pregnant women with placental insufficiency (PI).Materials and Methods: The PI was manifested as the intrauterine growth restriction syndrome of fetus (IUGR) in the third pregnancy trimester. The control group consisted of 20 women with uncomplicated pregnancy in the same term. The blood concentrations of melatonin, proinflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-β (IL-1-β), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4), and interleukin-10 (IL-10), were studied.Results: The concentration of melatonin was found to decrease significantly if pregnancy was complicated by intrauterine fetal growth retardation (study group −126.87 ± 14.87 pg/ml, control group −231.25 ± 21.56 pg/ml, p < .001). The levels of proinflammatory cytokines in the study group were significantly higher as compared with the control group (TNF-α: study group −10.05 ± 1.35 pg/ml, control group −5.60 ± 1.50 pg/ml, p < .05; IL-1-β: study group −14.67 ± 2.13 pg/ml, control group −3.96 ± 0.92 pg/ml, p < .001; IL-6: study group −6.91 ± 0.99 pg/ml, control group −2.69 ± 0.99 pg/ml, p < .05). The same is true about anti-inflammatory cytokines (IL-4: study group −5.97 ± 0.50 pg/ml, control group −3.74 ± 0.62 pg/ml, p < .05; IL-10: study group −11.40 ± 1.50 pg/ml, control group −4.70 ± 3.20 pg/ml, p < .001). A moderate negative correlation between melatonin and IL-1-β in the group with PI (r = −0.3776, p = .0097), a closed negative correlation between the same indexes in the control group (r = −0.6785, p = .001), and a moderate negative correlation between melatonin and TNF-α (r = −0.4908, p = .02) were found.Conclusions: The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. Strengthening of the proinflammatory immunity shown as the increasing of the levels of TNF-α, IL-1-β, and IL-6 levels is also present in case of IUGR. Increase of the serum concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of compensatory mechanisms, which decrease the risk of premature labor.

Spectrum of anti-inflammatory cytokines in pregnant women with placental insufficiencyand fetal growth retardation

Spectrum of anti-inflammatory cytokines in pregnant women with placental insufficiencyand fetal growth retardation

The effects of zinc supplementation on inflammatory parameters in pregnant women with impaired glucose tolerance: a randomized placebo controlled clinical trial

Pregnancy is hyperglycemic cycle of life and usually associated with insulin resistance from mid- gestation. Previous studies indicate that abnormal production of some proteins secreted from adipocytes (adipokines) encloses in pathogenesis of insulin resistance and gestational diabetes mellitus (GDM). It is proven that maternal zinc deficiency affects glucose metabolism, but the interaction between zinc and adipokines secretion are not well understood. This study aims to evaluate the effect of zinc supplementation on Vaspin and IL-6 levels in pregnant women with impaired glucose tolerance (IGT). In this matched, placebo controlled double blind clinical trial, 46 pregnant women with impaired glucose tolerance were randomly distributed to zinc (n=23) and placebo (n=23) groups and received 30 mg/day zinc gluconate or placebo for eight regular weeks. The study was conducted in Shabestar district, North West of Iran. Serum Vaspin and IL-6 levels were assessed before and after intervention. There was a significant decrease in Vaspin and IL-6 levels in zinc group (p= 0.004, p= 0.034, respectively). Further, changes in fasting Vaspin levels had a positive correlation with change in fasting IL-6 levels in both zinc (r= + 0.820, p<0.001) and placebo (r= + 1.000, p<0.001) groups. According to enhancement of inflammatory cytokines in pregnant women with IGT, zinc may be considered as a complimentary supplement together with medical management in patients with IGT and GDM. However, further studies with greater sample size and extended periods of intervention are needed to make definite conclusion.

CHANGES OF THE SLEEP, HORMONAL BALANCE AND PROFILE OF CYTOKINES IN PREGNANT WOMEN WITH PLACENTAL INSUFFICIENCY

Objective – to establish the correlation between the placental insufficiency, sleep disorders and pro- and anti-inflammatory part of the immune system by questioning, studying of the levels of melatonin, placental hormones and pro- and anti-inflammatory cytokines in pregnant women with placental insufficiency.Materials and methods. 80 pregnant women with placental insufficiency, manifesting as intrauterine fetal growth restriction (IUGR) of II-III degree in the 3rd pregnancy trimester (study group) and 30 women with normal clinical flow of pregnancy (control group) were questioned. 46 patients from study group and 20 patients from control group women were examined further: the studying of the blood plasma concentrations of melatonin, placental hormones (placental lactogen, free estriol), pro-inflammatory cytokines, such as tumor necrotizing factor-α (TNF-α), interleukin-1-β (IL-1-β), interleukin-6 (IL-6), and anti-inflammatory cytokines, such as interleukin-4 (IL-4) and interleukin-10 (IL-10), was conducted.Results and the discussion. Questioning showed that pregnant women with placental insufficiency (PI) in 86% cases experience the sleep disorders starting from pregnancy term 12-22 weeks (healthy pregnant women – mostly after 30 weeks, 57% cases), more commonly wake up 2 or more times per night (71% of positive answers, in control group – 23%), and 3 or more times per week (78% of positive answers, in control group – 17%). It also has been established that concentration of melatonin significantly decreases, if the pregnancy is complicated by intrauterine fetal growth restriction (study group – 126,87±14,87 pg/ml, control group – 231,25±21,56 pg/ml, p&lt;0,001). The levels of pro-inflammatory cytokines in the study group were significantly higher, comparing with the control group (TNF-α: study group – 10,05±1,35 pg/ml, control group – 5,60±1,50 pg/ml, p&lt;0,05; IL-1-β: study group – 14,67±2,13 pg/ml, control group – 3,96±0,92 pg/ml, p&lt;0,001; IL-6: study group – 6,91±0,99 pg/ml, control group – 2,69±0,99 pg/ml, p&lt;0,05). The same is true about anti-inflammatory cytokines (IL-4: study group – 5,97±0,50 pg/ml, control group – 3,74±0,62 pg/ml, p&lt;0,05; IL-10: study group – 11,40±1,50 pg/ml, control group – 4,70±3,20 pg/ml, p&lt;0,001). We did not find significant difference in hormonal concentrations between groups.Conclusions. Sleep disorders in pregnant women with placental insufficiency appear earlier and seem to be more expressed then in healthy pregnant women. The blood level of melatonin significantly decreases in case of placental insufficiency, manifested as intrauterine fetal growth restriction. The strengthening of the pro-inflammatory immunity, shown as the increasing of the levels of TNF-α, IL-1-β and IL-6, is also present in case of IUGR. The rising of the plasma concentration of the anti-inflammatory cytokines, such as IL-4 and IL-10, in our opinion, can be explained by activation of the mechanisms of compensation, which decrease the risk of premature labor.

89. Sleep variability is associated with inflammatory cytokines in pregnant women

Extreme variability in sleep duration and/or fragmentation impacts physiology and disease risk. Pregnant women have sleep variability given the changes that take place following conception. No investigations have examined the degree to which pregnant women experience sleep variability nor have any examined whether sleep variability results in immunological changes important for a successful pregnancy. Sleep diary and actigraphy-assessed sleep data collected from 168 pregnant women at 10–12 weeks’(T1), 14–16 weeks’(T2), and 18–20 weeks’(T3) gestation were assessed for intra-individual variability, estimated from each subject’s standard deviation on diary (D) and actigraphy (A) measures. Morning blood samples for assay of cytokines were collected. Greater variability in both D-and A-sleep variables were associated with higher circulating cytokine concentrations. At T1 greater variability in D-assessed sleep efficiency ( r = .29, p = .03) was associated with higher IL-6; greater variability in TIB was associated with higher IL-6 ( r = .26, p = .05) and TNF- α ( r = .23, p = .04). At T3 greater variability in D- and A-assessed sleep latency was associated with higher IL-6 ( r = .30, p = .01; r = .32, p = 01); D WASO was associated with lower TNF- α ( r = −.24, p = .03). Sleep variability appears to be a stressor that could increase in circulating inflammatory markers and adverse pregnancy outcomes. Importantly it is a modifiable stressor that can be intervened upon.

Imbalanced anti-H1N1 immunoglobulin subclasses and dysregulated cytokines in hospitalized pregnant women with 2009 H1N1 influenza and pneumonia in Shenyang, China

Influenza virus can cause an acute respiratory illness of variable intensity. In our study, we describe the clinical and immunological characteristics of pregnant and nonpregnant women who were hospitalized with 2009 H1N1 influenza and pneumonia in Shenyang, China, from November 2009 to January 2010. Forty-two female patient infected with H1N1 were divided into groups according to pregnancy. Clinical data were collected. Cytokines and anti-H1N1 IgG subclasses were detected. We observed significant lymphopenia, hypoproteinemia, reduced CD4(+)T cell counts and CD4(+)/CD8(+) ratios, reduced anti-H1N1 IgG subclasses IgG2 and IgG3 constituent ratios, elevated C reactive protein and interleukin-10 levels with regard to nonpregnant H1N1 group. Compared with the healthy pregnant group, the pregnant H1N1 group showed elevated aspartate aminotransferase and glutamic alanine aminotransferase levels, an increased interferon-gamma and interleukin-10 levels and reduced anti-H1N1 IgG subclasses IgG2, IgG3 and IgG4 combination ratios. There was a statistically significant association between imbalanced anti-H1N1 immunoglobulin subclasses and dysregulated cytokines in pregnant women with H1N1 infection.

PP062. Silibinin modulates NF-kB pathway and proinflammatory cytokines production by mononuclear cells of preeclamptic women

Pre-eclampsia (PE) is a complication of human pregnancy characterized by hypertension and proteinuria after 20 weeks of gestation. In addition to increased activation of monocytes and granulocytes, there is an elevated production of proinflammatory cytokines in pregnant women with PE. The nuclear transcription factor-kB (NF-kB) is present in the cells of the immune system and is responsible for transcription of genes related to inflammation. Whereas the PE is associated with intense inflammatory response, the use of substances modulating the activity of NF-kB factor could be useful in alleviating the inflammation present in these patients. Silibinin is the main component of silymarin, a polyphenolic extract obtained from fruits and seeds of Sylibum marianum with potent hepatoprotective, anti-inflammatory and anti-fibrotic activities. The objective of this study was to assess whether silibinin modulates the activity of NF-kB and the production of inflammatory cytokines by mononuclear cells of patients with PE. We evaluated 34 pregnant women with PE, 20 normotensive pregnant women (NT) and 15 non-pregnant women (NP). Mononuclear cells (PBMC) were obtained from peripheral blood and cultured in the presence or absence of silibinin (50uM) and stimulated with 1ug/mL of lipopolysaccharide (LPS) for 18h. The supernatant was employed for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1β) by enzyme immunoassay. The cells were also cultured for 30min to perform the extraction and determination of the nuclear activity of NF-kB. The results showed increased endogenous activation of NF-kB in PBMC of the PE group compared with the NT and NP groups. We also observed increased production of TNF-α and IL-1β by non-stimulated PBMC in the PE group compared with NT and NP groups. A positive correlation between NF-kB activity and endogenous production of TNF-α (r=0.6509; p=0.0047) or IL-1 b (r=0.5106; p=0.0304) was observed in the PE group. Silibinin showed an anti-inflammatory activity by inhibiting the spontaneous and LPS-stimulated NF-kB activation as well as the production of inflammatory cytokines in all the groups studied. Patients with PE showed a greater activation of PBMC cells compared with NT women. Silibinin showed modulatory activity on the inflammatory response by downregulation of NF-kB activation as well as TNF-α and IL-10 production. FAPESP 2010/00776-0.