scholarly journals CHANGES IN THE ACTIVITY OF INDUCIBLE NO-SYNTHASE AND ARGINASE, THEIR RELATIONSHIP WITH THE LEVEL OF PRO- AND ANTI-INFLAMMATORY CYTOKINES IN CERVICAL MUCUS IN PREGNANT WOMEN, WHO UNDERWENT IVF AND ARE AT RISK OF PRETERM CHILDBIRTH

2021 ◽  
Vol 21 (3) ◽  
pp. 21-25
Author(s):  
V. K. Likhachov ◽  
Ya. V. Shymanska ◽  
L. M. Dobrovolska ◽  
O. Ye. Akimov ◽  
O. H. Makarov
Keyword(s):  
At Risk ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
No Synthase ◽  
Cervical Mucus ◽  
Arginase Activity ◽  
Vitro Fertilization ◽  
Inducible No Synthase ◽  
Anti Inflammatory

Introduction. Nitric oxide (NO) produces a wide range of bioregulatory effects. Imbalance in the ratio of the activity of inducible NO-synthase and arginase in favor of iNOS can lead to a pro-inflammatory reaction. At the risk of preterm childbirth, the content of proinflammatory cytokines increases both at the local and systemic levels. The aim of this work is to study the relationship between changes in the content of pro- and anti-inflammatory cytokines and the activity of inducible NO-synthase and arginase in the cervical mucus of women with in vitro fertilization (IVF), who are at risk of preterm childbirth. Materials and methods. The test group (TG) included 37 women, who underwent IVF and presented prognostic signs, indicating a high risk of preterm birth in the future. The control group (CP) consisted of 20 healthy pregnant women, who did not undergo assisted reproductive technologies. We determined the indicators of inducible NO-synthase activity and total arginase activity, as well as the level of pro- and anti-inflammatory cytokines in the mucus of the cervical canal of the participants at their 28-34 weeks of pregnancy. Results and discussion. The activity of iNOS in TG significantly increased (in 2.57 times) compared to healthy pregnant women (CP), while the activity of arginase, on the contrary, decreased significantly (in 1.91 times). There was a significant increase in the levels of pro-inflammatory cytokines INF-γ and TNF-α in the TG women, while they demonstrated the significantly reduced concentration of anti-inflammatory cytokine IL-10. In cervical mucus taken from TG women, positive correlations were found between an increase in the concentration of the proinflammatory cytokine INF-γ and an increase in iNOS activity, between a decrease in IL-10 levels and arginase activity, and a negative relationship between an increase in iNOS activity and a decrease in arginase activity. Conclusions. The detected cytokine imbalance in pregnant women, who underwent in vitro fertilization and were at risk of preterm childbirth, together with a impaired ratio of iNOS and arginase, indicates an inappropriate level of immunosuppression. These immune changes, by activating cellular responses of maternal immunity, can contribute to preterme childbirth.

scholarly journals DIFFERENTIATION FACTORS OF M1 AND M2 SUBPOPULATIONS OF DECIDUAL MACROPHAGES IN PREGNANT WOMEN WITH PREECLAMPSIA, THEIR IMBALANCE AND WAYS TO CORRECT IT

2020 ◽  
Vol 20 (3) ◽  
pp. 14-19
Author(s):  
V. L. Vashchenko ◽  
V. K. Likhachov ◽  
O. Ye. Akimov ◽  
O. O. Taranovska
Keyword(s):  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
No Synthase ◽  
Cervical Mucus ◽  
Tnf Α ◽  
Before And After ◽  
Placental Site ◽  
Anti Inflammatory ◽  
The Difference ◽  
The Impact

According to the literature, inappropriate polarization of decidual macrophages is associated with abnormal pregnancy conditions such as spontaneous abortion, premature childbirth, preeclampsia, foetal growth retardation, etc.; therefore, studying the relationship between subpopulations of decidual macrophages and factors promoting their production in women with preeclampsia is of great clinical relevance. The purpose of this study was to identify the features of differentiation in subpopulations M1 and M2 of decidual macrophages in pregnant women with preeclampsia and to assess the impact of factors promoting their induction. Materials and methods. The concentrations of pro- and anti-inflammatory cytokines (TNF-α, INF-γ, IL-10) and the activity of iNOS and arginase in cervical mucus in pregnant women with preeclampsia were studied in comparison with the corresponding indicators in healthy pregnant women, with subsequent comparison of these indicators with the number of decidual macrophages M1 and M2 in the placentas of the examined women. We determined the concentration of cytokines by using immunoassay. NO synthase activity was determined by the difference in nitrite concentration before and after cervical mucus incubation. The total arginase activity was assessed by the difference in the concentration of L-ornithine before and after incubation in phosphate buffered saline, which contained L-arginine. Immunohistochemical study of macrophages M1 and M2 in placental tissue was carried out in the pathomorphological laboratory "CSD Health Care" (Kiev). A total of 62 pregnant women were examined: the control group included 30 healthy pregnant women who did not have risk factors for preeclampsia and unimpaired circulation in the uterine spiral arteries in the area of ​​the placental site at 18-20 + 6 weeks of gestation. The study group included 32 pregnant women at high risk to develop preeclampsia, with impaired circulation in the uterine spiral arteries in the area of ​​the placental site at 18-20 + 6 weeks of gestation; 14 of them then developed preeclampsia. Results. In pregnant women with preeclampsia, the balance of pro- and anti-inflammatory cytokines is impaired in favour of TNF-α and INF-γ with a decrease in IL-10 content that results in an imbalance in the activity of enzymes regulating the L-arginine metabolism with the following increase in iNOS activity. The activity of arginine is significantly reduced. In the placentas of women with preeclampsia, the content of decidual macrophages M1 phenotype is 1.7 times higher than their number in healthy women, while the content of macrophages M2 phenotype, on the contrary, goes down in 1.5 times. The study has shown that the predominance of decidual M1 macrophages in women with preeclampsia occurs due to the stimulating effect of INF-γ and the activation of inducible NO-synthase. This imbalance of decidual macrophages in favour of the M1 subpopulation is likely to cause the progression of endothelial dysfunction, manifestation of preeclampsia, and dysfunction of the placenta in the second trimester and in the early phase of the third trimester of gestation.

scholarly journals IMPACT OF PREVENTIVE THERAPY ON REGULATING MECHANISMS OF DECIDUAL MACROPHAGE POLARIZATION IN PREGNANT WOMEN WITH HIGH RISK OF PREECLAMPLSIA

2021 ◽  
Vol 74 (9) ◽  
pp. 2123-2127
Author(s):  
Volodymir K. Likhachov ◽  
Viktoriya L. Vashchenko ◽  
Olena О. Taranovska
Keyword(s):  
High Risk ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Vitamin D3 ◽  
Macrophage Polarization ◽  
Preventive Therapy ◽  
Cervical Mucus ◽  
Arginase Activity ◽  
M2 Macrophages ◽  
Anti Inflammatory

The aim: This study was aimed at analyzing the impact of preventive therapy for pregnant women at a high risk to develop preeclampsia on the normalization of the mechanisms of decidual macrophage polarization. Materials and methods: The methodology was designed to obtain data on the content of pro- and anti-inflammatory cytokines and indicators of nitric oxide and arginase metabolism in cervical mucus. The ration between M1 / M2 decidual macrophages in the placenta was determined by applying immunohistochemical methods. The effectiveness of the proposed therapy for the secondary prevention of preeclampsia (metformin, vitamin D3 and corvitin) was evaluated. Results: Pregnant women with preeclampsia showed the imbalance between pro- and anti-inflammatory cytokines in favour of TNF-α and INF-γ under the decrease in IL-10 that results in an imbalance in the activity of enzymes regulating L-arginine metabolism, with increased iNOS activity and decreased arginine activity. In the placentas of the pregnant women with preeclampsia, in contrast to the healthy pregnant women, M1 decidual macrophages are found as predominant. The women, who received the course of the preventive therapy with metformin, vitamin D3 and corvitin, showed a decrease in the concentration of pro-inflammatory cytokines and an increase in anti-inflammatory cytokine IL-10, normalization of the balance between iNOS and arginase activity, and the normalization of the M1 / M2 macrophages ratio. Conclusions: Normalization of the balance between pro- and anti-inflammatory cytokines, iNOS and arginase activity in cervical mucus, the ratio between decidual M1 and M2 macrophages as results of the therapy proposed reduce the incidence of preeclampsia and associated complications.

Evaluation of the cytokin status of women with miscarriage

2019 ◽  
pp. 59-63
Author(s):  
N. Skrypchenko ◽  
◽  
I. Vorobyova ◽  
T. Mazur ◽  
V. Tkachenko ◽  
...  
Keyword(s):  
Immune Response ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Cervical Mucus ◽  
Enzyme Analysis ◽  
Control Group ◽  
Inflammatory Reactions ◽  
Tnf Α ◽  
Anti Inflammatory

During pregnancy, a unique new equilibrium state appears between the systems of the specific and nonspecific mothers immunity. Besides, the cytokine cascade is launched, which includes proinflammatory and anti-inflammatory factors of influence. The balance between these two groups of mediators determines the nature of the course and outcome of the gestation process. The objective: to determine the role of mediators of pro-inflammatory and anti-inflammatory reactions of gestation intercourse in patients with miscarriage. Materials and methods. The main group (the first group) was made up of 153 pregnant women with miscarriage. The control group (the second group) consisted of 25 relatively healthy women with a physiological course of pregnancy and a complcated obstetric and gynecological anamnesis, with one and more physiological births in anamnesis. The concentration of cytokines IL-1 β, IL-6, IL-8, IL-10, TNF- α in the blood and their content in cervical mucus by solid-phase immune-enzyme analysis was determined. Results. Consequences of previous pregnancies having a background of inflammatory complications of genital and extragenital genesis create conditions for long-term persistence of latent infection, including in the uterine cavity and cervical canal, followed by infection of the fetus, and contribute to the development of immune imbalance during gestation, which leads to a cascade of homeostasis disorders with the development of complications of the pregnancy intercourse and perinatal pathology. Thus, the presence of clinical symptoms of the threat of premature abortion occurs in the context of an increase in the concentration of proinflammatory cytokines (IL-6, IL-8, TNF- α and IL-1 β) in serum.Reducing the concentration of IL-10 in non-pregnant women, relative to such in control group, throughout the entire pregnancy in the blood and its content in cervical mucus indicates a violation of the balance of pro– and anti-inflammatory cytokines in the direction of pro-inflammatory reactions and violation of the local immune response. Conclusions. In women with a loss in the first trimester there is a pro-inflammatory activity of the immune response, which is an important pathogenetic factor in the development of abortion in different gestational periods. Key words: miscarriage, proinflammatory cytokines, anti-inflammatory cytokines.

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

scholarly journals N-palmitoyl-D-glucosamine, A Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice

2021 ◽  
Vol 22 (3) ◽  
pp. 1491 ◽  
Author(s):  
Monica Iannotta ◽  
Carmela Belardo ◽  
Maria Consiglia Trotta ◽  
Fabio Arturo Iannotti ◽  
Rosa Maria Vitale ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Inflammatory Cytokines ◽  
Lipid A ◽  
Saturated Fatty Acids ◽  
Structural Similarity ◽  
Antagonistic Activity ◽  
Critical Function ◽  
Anti Inflammatory

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo. This study aimed to show the potential use of N-palmitoyl-D-glucosamine (PGA), a bacterial molecule with structural similarity to the lipid A component of LPS, which could be useful for preventing LPS-induced tissue damage or even peripheral neuropathies. Molecular docking and molecular dynamics simulations showed that PGA stably binds MD-2 with a MD-2/(PGA)3 stoichiometry. Treatment with PGA resulted in the following effects: (i) it prevented the NF-kB activation in LPS stimulated RAW264.7 cells; (ii) it decreased LPS-induced keratitis and corneal pro-inflammatory cytokines, whilst increasing anti-inflammatory cytokines; (iii) it normalized LPS-induced miR-20a-5p and miR-106a-5p upregulation and increased miR-27a-3p levels in the inflamed corneas; (iv) it decreased allodynia in peripheral neuropathy induced by oxaliplatin or formalin, but not following spared nerve injury of the sciatic nerve (SNI); (v) it prevented the formalin- or oxaliplatin-induced myelino-axonal degeneration of sciatic nerve. SIGNIFICANCE STATEMENT We report that PGA acts as a TLR4 antagonist and this may be the basis of its potent anti-inflammatory activity. Being unique because of its potency and stability, as compared to other similar congeners, PGA can represent a tool for the optimization of new TLR4 modulating drugs directed against the cytokine storm and the chronization of inflammation.

Peculiarities of pregnancy and delivery course in women after the application of assisted reproductive technologies against obesity (Based on the retrospective analysis)

2018 ◽  
pp. 122-126
Author(s):  
I.A. Zhabchenko ◽  
◽  
O.R. Sudmak ◽  
Keyword(s):  
In Vitro Fertilization ◽  
Pregnant Women ◽  
Retrospective Analysis ◽  
Perinatal Outcomes ◽  
Reproductive Technologies ◽  
Ischemic Lesion ◽  
Vitro Fertilization ◽  
Pregnancy And Delivery

The objective: to study the structure and frequency of complications of pregnancy, deliveries and perinatal outcomes in three groups of women: women with infertility and obesity, treated by application of in vitro fertilization (hereinafter IVF), pregnant women after IVF application with normal body weight, and pregnant women on the background of obesity which did not have an infertility in past history. Materials and methods. A retrospective analysis of 221 case histories of pregnancies and labors in women who were treated and gave birth in the Pregnancy and delivery pathology Department of SI «Institute of Pediatrics, Obstetrics and Gynecology named after Acad. O. M. Lukyanova of NAMS of Ukraine» for 2012 – 2016 years was carried out. Results. The overwhelming majority of pregnant women after IVF on the background of obesity are primaparas, who have a complicated obstetric history, hormonal changes in the form of progesterone deficiency predominantly and chronic inflammatory processes. Pregnancy with a combination of infertility, treated by the means of IVF application, and obesity, in most cases is accompanied by a long-term threat of termination of pregnancy (48.8%), threatening preterm deliveries (56%), placental dysfunction (41.5%), premature rupture of the amniotic membranes (41.5%), other problems during pregnancy, at the same time, every second woman (58.5%) had a combination of several complications, and required a long-term and repeated inpatient treatment (53.7%). The specific gravity of surgical delivery was 90%, and 16.2% of such deliveries were complicated by pathological blood loss. The number of preterm deliveries was 17.1%, with perinatal losses up to 11.3‰. Among full-term newborns 21.3% of newborns had malnutrition of the I degree and 17% of them had hypoxic-ischemic lesion of CNS. Conclusion. The course of pregnancy, delivery and the postpartum period in the studied contingent of women has a significant frequency of complications, mainly the coinciding ones, which affects on the consequences of perinatal outcomes and requires further study of this problem and the development of differentiated algorithms for antenatal observation. Key words: pregnancy, obesity, in vitro fertilization, complications, delivery, newborn.

scholarly journals Plasma levels of melatonin, certain cytokines and placental growth factor at non-pharmacological correction of pineal function in pregnant women with intrauterine growth restriction

2020 ◽  
Vol 8 (2) ◽  
Author(s):  
A. Berbets ◽  
Keyword(s):  
Immune System ◽  
Growth Factor ◽  
Pineal Gland ◽  
Pregnant Women ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Placental Growth Factor ◽  
Placental Insufficiency ◽  
Tnf Α ◽  
Anti Inflammatory

The pineal gland produces the important hormone melatonin, the level of which in the blood of pregnant women decreases in case of placental insufficiency. The effect of dysfunction of the pineal gland on the immune system of pregnant women and on the angiogenic activity of the placenta during pregnancy remains insufficiently studied. Objective: to establish the effect of our method of non-drug correction of function of pineal gland on the state of the cytokine part of the immune system and on the synthesis of placental growth factor (PlGF) in pregnant women with placental insufficiency manifesting as fetal intrauterine growth restriction (IUGR). Material and methods. 46 pregnant women with IUGR at 30-36 weeks of gestation were examined. The group was divided into two subgroups: with non-drug correction of the pineal gland function (n = 25) and without correction (n = 21). The method of correction included a set of measures of following of lighting regimen, activity and sleep for 14 days. The control group consisted of 20 women with uncomplicated pregnancy. Levels of melatonin, PlGF, TNF-α, IL-1β, IL-6, IL-4, IL-10 were determined in the venous blood by enzyme-linked immunosorbent assay. Results. It was established that the concentration of melatonin in the blood of pregnant women with IUGR was significantly reduced, as well as the concentration of PlGF (p < 0.01). Significant changes were also found in pregnant women with placental insufficiency, namely, increased concentrations of proinflammatory cytokines, such as TNF-α (p < 0.05), IL-1-β (p < 0.001) and IL-6 (p < 0.05), comparing to healthy pregnant women. Also, in the group of pregnant women with IUGR the levels of anti-inflammatory cytokines IL-4 (p <0.001) and IL-10 (p < 0.001) were elevated in comparison to the control group. After application of the developed complex of non-drug correction of pineal gland function, the concentration of melatonin in the blood of pregnant women in the subgroup of correction increased significantly, comparing to the subgroup without correction (p < 0.001), as well as the level of PlGF (p < 0.05). Also, significantly lower levels of proinflammatory cytokines TNF-α, IL-1-β and IL-6 were observed in pregnant women in the subgroup of correction (p < 0.01). Regarding anti-inflammatory cytokines, under the influence of the developed complex of measures there was a decrease in the level of IL-4 and an increase in the level of IL-10 (p < 0.01). Conclusions. When the measures, aimed at non-drug correction of function of pineal gland, are applied in pregnant women with placental insufficiency, manifested as IUGR, the following changes are observed: increased of plasma levels of melatonin and placental growth factor, decreased of levels of proinflammatory cytokines. We suggest that the pineal gland exerts its effect on the immune system through melatonin, which moderates the activity of pro- and anti-inflammatory cytokines, thereby reducing the influence of inflammation on placental tissue, what results in increasing of concentrations of placental growth factor in the blood of pregnant women.

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