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 ◽  

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.

2019 ◽  
pp. 59-63
Author(s):  
N. Skrypchenko ◽  
◽  
I. Vorobyova ◽  
T. Mazur ◽  
V. Tkachenko ◽  
...  

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.


2006 ◽  
Vol 100 (4) ◽  
pp. 1124-1133 ◽  
Author(s):  
Frank Zaldivar ◽  
Jessica Wang-Rodriguez ◽  
Dan Nemet ◽  
Christina Schwindt ◽  
Pietro Galassetti ◽  
...  

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18–30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1α, IL-2, IFN-γ, and TNF-α), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes ( P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-α, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-γ and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.


2021 ◽  
Vol 17 (7) ◽  
pp. 534-551
Author(s):  
K.P. Zak ◽  
V.V. Popova ◽  
V.L. Orlenko ◽  
O.V. Furmanova ◽  
N.D. Tronko

The paper analyzes the current literature data and the results of our own researches concerning the state of the cytokine network: pro- and anti-inflammatory cytokines (interleukin (IL) 1α, IL-1β, IL-4, IL-6, IL-10, IL-17 and tumor necrosis factor (TNF) α), α- and β-chemokines, including IL-8 and IL-16, as well as adipokines (leptin and adiponectin) in the peripheral blood of patients with type 2 diabetes (T2D) with normal and increased body weight/obesity. It has been shown that patients with T2D are cha­racterized by an increased content of proinflammatory cytokines (IL-1, IL-6, IL-17, TNFα), α- and β-chemokines in the peripheral blood, including IL-8 and IL-16, as well as leptin with a decrease in adiponectin content. In lean patients (with body mass index (BMI) < 25.5 kg/m2) compared to lean normoglycemic individuals from the control group (BMI < 25.5 kg/m2), there is a small but significant increase in IL-1β, IL-6, IL-17, TNFα and leptin, which, as BMI increases, significantly increases in severe obesity (BMI > 30.0 kg/m2), especially in obese women (BMI > 35.0 kg/m2). Similarly, an increase in proinflammatory cytokines is observed in normoglycemic people, but not as signifi­cant as in T2D. Less clear data were obtained when during determination of the anti-inflammatory cytokines IL-4 and IL-10, which is explained by a significant polymorphism of their genes, and both protective and compensatory effects on pro-inflammatory cytokine rise. In T2D patients, especially those with obesity, there is an increase in the leptin level and a decrease in the adiponectin content. The severity of the course and the percentage of mortality are closely associated with the BMI of patients. The effectiveness of the fight against an increase in the incidence of T2D should be primarily aimed at preventing obesity, and in case of already developed T2D — at reducing concomitant obesity. The analysis of the data presented also suggests that a sharp increase in the content of pro-inflammatory cytokines (so called cytokine storm) observed in patients with T2D and obesity infected with COVID-19, is a consequence of the summation and potentiation of already existing inflammatory process.


Author(s):  
V. L. Vashchenko ◽  
V. K. Likhachov ◽  
O. Ye. Akimov ◽  
O. O. Taranovska

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.


2011 ◽  
Vol 58 (4) ◽  
Author(s):  
Irena Tam ◽  
Krystyna Stępień

A large body of evidence suggests that epidermal melanocytes are an integral part of the skin immune system and can be considered immunocompetent cells. Recently, it has been reported that human melanocytes constitutively express Toll-like receptors and may be involved in the induction of several inflammatory cytokines. In the study the secretion of IL-1β, IL-6 and TNF-α by cultured normal melanocytes was investigated after stimulation with lipopolysaccharide. LPS increased the secretion of IL-1β in a dose-dependent manner. IL-1β stimulated release of IL-6 and TNF-α by melanocytes, whereas LPS activated production of TNF-α, but not of IL-6. These observations indicate that LPS can participate in the regulation of cytokine activity in normal human melanocytes and suggest that cytokines released by melanocytes could affect melanocytes themselves or/and other cells of the epidermis.


Author(s):  
Hanie Mahaki ◽  
Naghi Jabarivasal ◽  
Khosro Sardarian ◽  
Alireza Zamani

Background: Extremely low-frequency electromagnetic fields (ELF-EMFs) are abundantly produced in modern societies. In recent years, interest in the possible effects of ELF-EMFs on the immune system has progressively increased. Objective: To examine the effects of ELF-EMFs with magnetic flux densities of 1, 100, 500, and 2000 µT on the serum levels of interleukin (IL)-9, IL-10, and tumor necrosis factor-alpha (TNF-α). Methods: 80 adult male rats were exposed to ELF-EMFs at a frequency of 50 Hz for 2 h/day for 60 days. The serum cytokines were measured at two phases of pre- and post-stimulation of the immune system by human serum albumin (HSA). Results: Serum levels of IL-9 and TNF-α, as pro-inflammatory cytokines, were decreased due to 50 Hz EMFs exposure compared with the controls in the pre- and post-stimulation phases. On the contrary, exposures to 1 and 100 µT 50 Hz EMFs increased the levels of antiinflammatory cytokine, and IL-10 only in the pre-stimulation phase. In the post-stimulation phase, the mean level of serum IL-10 was not changed in the experimental groups. Conclusion: The magnetic flux densities of 1 and 100 µT 50 Hz EMFs had more immunological effects than EMFs with higher densities. Exposure to 50 Hz EMFs may activate anti-inflammatory effects in rats, by down-modulation of pro-inflammatory cytokines (IL-9 and TNF-α) and induction of the anti-inflammatory cytokine (IL-10).


2020 ◽  
Vol 10 (4) ◽  
pp. 362-368
Author(s):  
Irina Danusevich ◽  
Eldar Sharifulin ◽  
Uliana Nemchenko ◽  
Lyubov Kolesnikova

The objective of our study was to investigate the specific features of immune status indicators in women of reproductive age with chronic endometritis (CE) and reproductive disorders. Methods and Results: The observational study involved 81 women of reproductive age with reproductive disorders. The main group (MG) included 50 women with CE (mean age of 29.2±5.34 years). The control group (CG) consisted of 31 fertile women also of reproductive age(mean age of 30.7 ± 5.9 years). MG was divided into the following subgroups: Subgroup A (SubA) included 31 patients with verified CE and an isolated infectious agent from endometrial tissue: Subgroup B (SubB) included 19 patients with verified CE and the absence of an infectious agent in the endometrial tissue. Endometrial aspiration pipe biopsy was performed on days 4-9 of the menstrual cycle (middle proliferative phase) using a disposable intrauterine probe (Taizhou Kechuang Medical Apparatus Co., Ltd, China) followed by histological examination of endometrial tissue. Laboratory diagnostics for sexually transmitted infections (STIs) was performed using the bacterial culture method. For the diagnosis of viral infection (HPV, HSV, CMV), cervical samples were studied using PCR. If STIs were detected, the patients were excluded from further research. Ultrasound examination of the pelvic organs was performed using the Aloka-5500 device with a 7MHz vaginal probe in two-dimensional visualization mode. The concentration of cytokines (IL-1β, INF-γ, TNF-α, ILs-4,6,8,10) in the endometrium was determined using the Protein Contour test systems (Saint Petersburg) and Multiskan EX ELISA Analyzer (Germany). The percentages and absolute counts of blood lymphocytes (CD3+, CD3+/CD8+/CD45+, CD19+/CD45+, and CD16+/CD56+/CD45+ cells) were determined by the method of indirect immunofluorescence with monoclonal antibodies using the BD FACSCalibur flow cytometer (USA). We found a significant increase in the blood concentrations of CD3+ cells, CD3+/CD8+/CD45+ cells, and CD19+/CD45+ cells and a decrease in the levels of CD16+/CD56+/CD45+ cells, microbicidal activity of oxygen-dependent function of neutrophils, and phagocytic activity of neutrophils, as well as a significant decrease in the levels of IgA, IgM, and IRI in MG, compared to CG. In SubA, compared to SubB, we found a significant decrease in CD3+ cells and CD19+/C45+ cells and a slight increase in immunoregulatory index. The concentrations of tissue cytokines in women of MG were characterized by a 3-fold increase in the level of pro- and anti-inflammatory cytokines (IL-1β, ILs - 4, 6, 10, and INF-γ), and a 4-fold increase in the levels of TNF-α and IL-8, compared to CG. In SubA, in comparison with SubB, a significant decrease in anti-inflammatory cytokines (ILs-4,10) and chemokine IL-8 was revealed against the background of a significant increase in the concentrations of INF–γ and TNF–α. Conclusion: The results obtained indicate changes in the reactivity of the immune system in women with reproductive disorders and chronic inflammation in the endometrium. The most pronounced changes in the local immunity indicators are observed when opportunistic pathogens are detected in the endometrial tissue.


2004 ◽  
Vol 78 (24) ◽  
pp. 13697-13707 ◽  
Author(s):  
Alana M. Thackray ◽  
Andrew N. McKenzie ◽  
Michael A. Klein ◽  
Angus Lauder ◽  
Raymond Bujdoso

ABSTRACT The identity of pro- and anti-inflammatory cytokines in the neuropathogenesis of prion diseases remains undefined. Here we have investigated the role of anti-inflammatory cytokines on the progression of prion disease through the use of mice that lack interleukin-4 (IL-4), IL-10, IL-13, or both IL-4 and IL-13. Collectively our data show that among these anti-inflammatory cytokines, IL-10 plays a prominent role in the regulation of prion disease. Mice deficient in IL-10 are highly susceptible to the development of prion disease and show a markedly shortened incubation time. In addition, we have correlated cytokine gene expression in prion-inoculated IL-10−/− mice to wild-type-inoculated animals. Our experiments show that in the absence of IL-10 there is an early expression of tumor necrosis factor alpha (TNF-α). In wild-type prion-inoculated mice, the expression of TNF-α mRNA occurs at a later time point that correlates with the extended incubation time for terminal disease development in these animals compared to those that lack IL-10. Elevated levels of IL-13 mRNA are found at early time points in the central nervous system of prion-inoculated IL-10−/− mice. At terminal disease, the brains of wild-type mice inoculated with RML or ME7 are characterized by elevated levels of mRNA for the proinflammatory cytokines TNF-α and IL-1β, together with the anti-inflammatory cytokines IL-10, IL-13, and transforming growth factor beta. Our data are consistent with a role for proinflammatory cytokines in the initiation of pathology during prion disease and an attempt by anti-inflammatory cytokines to regulate the ensuing, invariably fatal pathology.


2002 ◽  
Vol 70 (2) ◽  
pp. 749-761 ◽  
Author(s):  
Abdul Q. Khan ◽  
Yi Shen ◽  
Zheng-Qi Wu ◽  
Thomas A. Wynn ◽  
Clifford M. Snapper

ABSTRACT Proinflammatory cytokines play a critical role in innate host defense against extracellular bacteria. However, little is known regarding the effects of these cytokines on the adaptive humoral response. Mice injected with a neutralizing anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb) at the time of primary immunization with intact Streptococcus pneumoniae (strain R36A) showed a substantial reduction in both the primary immunoglobulin G (IgG) response specific for the cell wall protein, pneumococcal surface protein A (PspA), as well as in the development of PspA-specific memory. In contrast, anti-TNF-α MAb injected only at the time of secondary immunization with R36A failed to alter the boosted anti-PspA response. TNF-α was required only within the first 48 to 72 h after primary immunization with R36A and was induced both by non-B and non-T cells and by lymphoid cells, within 2 to 6 h after immunization, with levels returning to normal by 24 h. Thus, the early innate release of TNF-α was critical for optimal stimulation of the subsequent adaptive humoral response to R36A. Additional proinflammatory (interleukin 1 [IL-1], IL-6, IL-12, and gamma interferon [IFN-γ]) as well as anti-inflammatory (IL-4 and IL-10) cytokines were also transiently induced. Mice genetically deficient in IL-6, IFN-γ, or IL-12 also showed a reduced IgG anti-PspA response of all IgG isotypes. In contrast, IL-4−/− and IL-10−/− mice immunized with R36A showed a significant elevation in the IgG anti-PspA response, except that there was decreased IgG1 in IL-4−/− mice. In this regard, a marked enhancement in the induction of proinflammatory cytokines was observed in the absence of IL-10, relative to controls. Ig isotype titers specific for the phosphorycholine determinant of C-polysaccharide were similarly regulated, but to a much more modest degree. These data suggest that proinflammatory and anti-inflammatory cytokines differentially regulate an in vivo protein- and polysaccharide-specific Ig response to an extracellular bacteria.


2016 ◽  
pp. 25-28
Author(s):  
J.M. Melnik ◽  
◽  
A.A. Shlyahtina ◽  

The article presents the predictors of placental dysfunction on the early stage of pregnancy. The objective: the search for prognostic markers and criteria for the occurrence of placental insufficiency in the early stages of the gestational process to optimize the pregnancy and labor with improved perinatal outcomes. Patients and methods. To solve this goal in the period from 2013 to 2015 were conducted a comprehensive survey of 334 pregnant women, which depending on the peculiarities of pregnancy and childbirth were divided into groups. The control group consisted of 236 pregnant women with uncomplicated gestational period, no morphological signs of placental dysfunction. The study group included 98 patients with a complicated pregnancy who had revealed violations of the fetal-placental relations, which was confirmed by morphological examination of the placenta in the postpartum period. Results. It was found that pregnant women with placental insufficiency in the first trimester of pregnancy have higher levels of interleukin-1B (IL-1v) and interleukin-3 (IL-3) in comparison with physiological pregnancy, as well as there is a direct significant correlation between IL-1v and pulsative index (PI) in the spiral (r=0.84) and uterine artery (r=0.77), and the inverse correlation between the level of IL-3 and PI in the terminal branches of the umbilical artery (r=-0.69). Verified an inverse relationship between the concentration of endothelin-1, the level of vascular endothelial growth factor (r=-0.87) and placental growth factor (r=-0.73), and also a direct link between the content of endothelin-1 and PI in spiral arteries (r=0.89), uterine artery (r=0.83) and the terminal branches of the umbilical artery (r=0.79). Conclusion. Thus, it is proven that early predictors of placental dysfunction can be considered the concentration of endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin-1, interleukin-3, and the indices of pulsative index. Key words: placental dysfunction, predictors, endothelin-1, vascular endothelial growth factor, placental growth factor, interleukin, pulsative index.


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