Impact of TNF-α profile in recurrent pregnancy loss pathogenesis: A patient based study from Assam

Begum, Anjuma; Mishra, Archana; Das, Chandana; Das, Sangeeta; Dutta, Ratul; Kashyap, Natasha; Bose, Purabi Deka; Bose, Sujoy

doi:10.1016/j.jri.2021.103430

Cited by 5 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…У ході досліджень нами виявлено суттєве пригнічення синтезу a 2 -мікроглобуліну фертильності в жінок із ХЕ [21]. За настання вагітності цей білок відіграє одну з провідних ролей у процесах інвазії трофобласту, і механізм його дії пов'язаний з активацією ряду прозапальних і протизапальних цитокінів, серед яких важливими є фактор некрозу пухлини альфа (ТNF-a), інтерферон гамма (INF-g), а також інтерлейкін 10 (IL-10) [1,16,23].…”

Section: оригінальні дослідженняunclassified

“…Враховуючи, що плодово-плацентарна тканина є напівалотрансплантатом, імунологічне її розпізнавання в ході вагітності разом із подальшою відповіддю імунної системи матері є необхідною умовою для успішного перебігу гестаційного процесу [2,11]. Це розпізнавання супроводжується зміною профілю секреції цитокінів активованими лімфоцитами, що призводить до збільшення продукування незапальних, нецитотоксичних інтерлейкінів (наприклад, IL-10) і зниження утворення запальних, цитотоксичних цитокінів (наприклад, IFN-g і TNF-a) [1,2]. У разі неадекватності цих змін превалювання прозапальних цитокінів може призводити до абортивного ефекту, опосередкованого цитотоксичною дією цих цитокінів на тканини ембріона [11,14].…”

Section: оригінальні дослідженняunclassified

“…Зростання рівня прозапальних цитокінів INF-g і TNF-a, на нашу думку, пов'язане з необхідністю протимікробного захисту в умовах хронічного запального процесу і свідчить про персистування внутрішньоматкової інфекції при ХЕ [17,18]. При цьому в разі настання вагітності надмірний синтез прозапальних цитокінів може стати причиною порушення міжклітинної взаємодії і призвести до неповноцінної гестаційної трансформації спіральних артерій [1,8,23].…”

Section: результати дослідження та їх обговоренняunclassified

“…Безпосередній вплив пов'язаний з цитолітичною дією TNF-a та INF-g на клітини плода і трофобласта, обумовленою активацією NK-та LAK-клітин [11,12]. Опосередкований вплив полягає в тому, що високі концентрації вказаних цитокінів запускають коагуляційну систему шляхом активації прямої протромбінази, що спочатку зменшує, а потім остаточно припиняє постачання крові до ембріона; це, зрештою, спричиняє самовільний викидень [1].…”

Section: результати дослідження та їх обговоренняunclassified

See 3 more Smart Citations

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

View full text Add to dashboard Cite

The incidence of chronic endometritis is more than twice higher the prevalence of other clinical forms of intrauterine pathology, leading to infertility, unsuccessful attempts of in vitro fertilization and spontaneous abortion. There is a lack of data on the alteration of pro- and anti-inflammatory cytokine production in chronic endometritis and their role in the subsequent development of miscarriage. Purpose - to investigate the levels of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), as well as the anti-inflammatory cytokine interleukin 10 (IL-10) in cervical mucus of women with chronic endometritis and to assess the impact of the developed comprehensive preconception treatment on normalizing cytokine disorders in these women. Materials and methods. The levels of pro-inflammatory cytokines TNF-α and INF-γ, as well as the anti-inflammatory cytokine IL-10, were determined using the enzyme-linked immunosorbent assay method in the cervical mucus of 426 women with chronic endometritis who were planning pregnancy. Among them, 168 patients (the Group I) received preconception comprehensive treatment, which included broad-spectrum antibacterial agents (azithromycin), hormonal estrogen-progestin therapy (Femoston 2/10) and L-arginine. The remaining 258 women (the Group II) did not receive treatment for chronic endometritis at the preconception stage. The control group consisted of 30 healthy individuals. Data analysis was performed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the mean (m). The Student’s t-test was applied, and probabilities were determined using the statistical program «STATISTICA» (StatSoft Inc., USA). Results. In the cervical mucus of women with chronic endometritis, an increase in the levels of pro-inflammatory cytokines INF-γ by 2.8 times (p<0.001) and TNF-α by 2 times (p<0.001) was detected, along with a 2-fold decrease in the concentration of the anti-inflammatory cytokine IL-10 (p<0.001). The shift in the cytokine balance towards pro-inflammatory cytokines is associated with a high frequency of miscarriage in these women. After the treatment of chronic endometritis, women had a 2.6 times lower level of INF-γ (p<0.05), a 2 times lower level of TNF-α (p<0.01), and a 1.7 times higher level of IL-10 (p<0.05) compared to untreated patients. Conclusions. Women with chronic endometritis experience a cytokine imbalance, characterized by an excessive increase in pro-inflammatory cytokines and a decrease in anti-inflammatory cytokines. Women with chronic endometritis who are planning pregnancy require comprehensive preconception treatment, which includes the administration of azithromycin, femoston 2/10 and L-arginine in addition to traditional preconception folate prophylaxis. This treatment, by promoting improved conditions for implantation, leads to a 15% increase in the pregnancy rate and a 1.9-fold reduction in the frequency of spontaneous abortion. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

show abstract

Section: оригінальні дослідженняunclassified

Section: результати дослідження та їх обговоренняunclassified

See 2 more Smart Citations

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Likhachov,

Taranovska

2023

UJPP

View full text Add to dashboard Cite

show abstract

“…The latter, in addition to their ability to potentiate aggressive immune responses, have a significant limiting effect on the processes of spiral vascular transformation [17,18]. TNF-α from decidual macrophages promotes the transformation of invasive trophoblasts into non-invasive ones, inhibits the migration of trophoblast cells, reduces their viability, thereby decreasing their resistance to the lytic eff ects of NK cells [18,19]. INF-γ stimulates NK cells and cytotoxic T lymphocytes, leading to the formation of lymphokine-activated killer cells capable of damaging trophoblasts, and also inhibits the production of a number of trophoblast growth factors [17][18][19].…”

Section: Introductionmentioning

confidence: 99%

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

Likhachov,

Taranovska

2023

Neonatol. hìr. perinat. med.

View full text Add to dashboard Cite

Few data regarding the levels of TNF-α, INF-γ and IL-10 in the cervical mucus of pregnant women with the past medicalhistory of chronic endometritis have been found. The abovementioned cytokines have the impact on the course of pregnancy as well as the processes of trophoblast invasion into the spiral arteries of the uterus. Deviations in their levels at the early stages of pregnancy may be associated with the development of preeclampsia at later stages.Purpose: to assess the levels of TNF, INF-γ and cytokine IL-10 in the cervical mucus of pregnant women with a past medicalhistory of chronic endometritis. Additionally, the study aims to determine their role in the development of preeclampsia andevaluate the eff ectiveness of comprehensive preconception treatment in preventing cytokine imbalance and the occurrence of gestational complications.Method and Materials. 135 pregnant women with the past medical history of chronic endometritis have been supervisedduring their pregnancy and received preconception treatment (Group I), as well as 168 women, whose pregnancy occurred in the presence of untreated chronic endometritis (Group II). The control group (CG) involved 20 healthy women. Preconception treatment included the administration of azithromycin, hormonal therapy with Femoston- Comb 2/10, and L-arginine aspartate in combination with folate prophylaxis. During the study, the principles of patient- centered care were followed in accordance with the requirements of the Tokyo Declaration of the World Medical Association, the International Recommendations of the Helsinki Declaration on Human Rights, the Convention on Human Rights and Biomedicine of the Council of Europe, the Laws of Ukraine, the Orders of the Ministry of Health of Ukraine and the requirements of the Ethical Code of the Ukrainian physician. The cytokine (TNF-α, INFγ, IL-10) analysis in the cervical mucus was performed at 5-, 17-18 and 32 weeks of pregnancy, using the enzyme- linked immunosorbent assay method with corresponding standard commercial reagent kits from the «Vector BEST» company. The obtained data were processed using mathematical statistical methods, calculating the mean sample values (M), variance (σ) and standard errors of the means (m). Student’s t-test was used for assessment and the likelihood ratio was calculated using the «STATISTICA» software (StatSoft Inc., USA).The paper is an excerpt from the initiative scientifi c research project of the Department of Obstetrics and Gynecology No.2 at Poltava State Medical University, entitled «Optimization of approaches to the management of pregnancy in women at high risk of obstetric and perinatal pathology» (State registration number 0122U201228, duration:10.2022-09.2027).Results. In pregnant women with a past medical history of chronic endometritis an increase in the levels of INF-γ in cervicalmucus by 2.1 times at 5-6 weeks (p<0.001), by 2.4 times at 17-18 weeks (p<0.001) and by 1.7 times at 32 weeks of pregnancy(p<0.001) compared to corresponding levels of this cytokine in healthy pregnant women, has been detected. Similarly, TNF-αwas by 4.3 times greater at 5-6 weeks of pregnancy compared to the values in the control group (p<0.001), by 3.3 times greater at 17-18 weeks of pregnancy (p<0.001) and by 4.4 times at 32 weeks of pregnancy (p<0.001). All pregnant women with a past medical history of chronic endometritis who had levels of INF-γ in the cervical mucus greater than 66.4 pg/ml and/or levels of TNF-α greater than 90.9 pg/ml at 5-6 weeks of pregnancy subsequently manifested preeclampsia (OR 2.01; 95 % CI [1.1-7.12]; p<0.05 and OR 1.8; 95 % CI [1.2-6.29]; p<0.05 respectively). The level of IL-10 in their cervical mucus was by 4 times higher than the control values at 5-6 weeks of pregnancy (p<0.0001); by 3.1 times higher at 17-18 weeks of pregnancy (p<0.0001) and by 3 times higher at 32 weeks of pregnancy (p<0.0001). This compensates for the increase in pro-infl ammatory cytokines, allowing the TNF-α/IL-10 ratio to remain at a level characteristic of healthy women throughout pregnancy. In treated women, the concentration of INF-γ is by 1.8 times lower than in untreated patients at 5-6 weeks of pregnancy (p<0.0001), by 2.1 times at 17-18 weeks of pregnancy (p<0.0001), and by 1.4 times at 32 weeks of pregnancy (p<0.0001). Similarly, TNF-α in cervical mucus was found to be lower by 3.6 times (p<0.01), 2.6 times (p<0.0001), and 4 times (p<0.001) respectively, in the specifi ed terms. This helps to avoid excessive production of the anti-infl ammatory cytokine IL-10.Conclusions. In women who got pregnant with untreated chronic endometritis, an increased production of cytokines INF-γand TNF-α at the early stages of pregnancy has been established. Comprehensive pregravidar treatment of chronic endometritis allows for the normalization of levels of anti-infl ammatory cytokines INF-γ and TNF-α at the beginning of gestation, which creates conditions for preventing the development of preeclampsia. This leads to a 1.9 times reduction in the frequency of this complication (OR 2.3; 95 % CI [1.25-4.31]; p<0.05), a 1.8 times decrease in the frequency of severe forms of preeclampsia (OR 4.64; 95 % CI [1.23-17.48]; p<0.05) and a delay in the average onset of its manifestations by 4.9 weeks (p<0.0001).

show abstract

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence

Stavros,

Panagopoulos,

Machairiotis

et al. 2024

Intl J Gynecology & Obste

View full text Add to dashboard Cite

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin‐6, tumor necrosis factor‐alpha, and interleukin‐10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

show abstract

Impact of TNF-α profile in recurrent pregnancy loss pathogenesis: A patient based study from Assam

Cited by 5 publications

References 33 publications

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in levels of pro- and anti-inflammatory cytokines in women with chronic endometritis and and the possibility of medically correcting these levels at the preconception stage

Changes in Cytokine Balance in Pregnant Women With Chronic Endometritis in the Past Medical History and Their Role in the Development of Preeclampsia

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence

Contact Info

Product

Resources

About