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.

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.

scholarly journals Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy

2021 ◽  
Vol 18 (16) ◽  
pp. 8538
Author(s):  
Maciej Kwiatek ◽  
Tomasz Gęca ◽  
Anna Kwaśniewska
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Control Group ◽  
Study Group ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Tgf Β1

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.

scholarly journals Cytokines in the blood of patients with type 2 diabetes mellitus depending on the level of overweight/obesity (literature review and own data)

2021 ◽  
Vol 17 (7) ◽  
pp. 534-551
Author(s):  
K.P. Zak ◽  
V.V. Popova ◽  
V.L. Orlenko ◽  
O.V. Furmanova ◽  
N.D. Tronko
Keyword(s):  
Type 2 Diabetes ◽  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Peripheral Blood ◽  
Control Group ◽  
Obese Women ◽  
Cytokine Network ◽  
Tnf Α ◽  
Anti Inflammatory

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.

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 Age and Sport Intensity-Dependent Changes in Cytokines and Telomere Length in Elite Athletes

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1035
Author(s):  
Maha Sellami ◽  
Shamma Al-muraikhy ◽  
Hend Al-Jaber ◽  
Hadaia Al-Amri ◽  
Layla Al-Mansoori ◽  
...  
Keyword(s):  
Immune Response ◽  
Telomere Length ◽  
Inflammatory Cytokines ◽  
Elite Athletes ◽  
Age Groups ◽  
Moderate Intensity ◽  
Necrosis Factor Alpha ◽  
Blood Samples ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Exercise-associated immune response plays a crucial role in the aging process. The aim of this study is to investigate the effect of sport intensity on cytokine levels, oxidative stress markers and telomere length in aging elite athletes. Methods: In this study, 80 blood samples from consenting elite athletes were collected for anti-doping analysis at an anti-doping laboratory in Italy (FMSI). Participants were divided into three groups according to their sport intensity: low-intensity skills and power sports (LI, n = 18); moderate-intensity mixed soccer players (MI, n = 31); and high-intensity endurance sports (HI, n = 31). Participants were also divided into two age groups: less than 25 (n = 45) and above 25 years old (n = 35). Serum levels of 10 pro and anti-inflammatory cytokines and two antioxidant enzymes were compared in age and sport intensity groups and telomere lengths were measured in their respective blood samples. Results: Tumor necrosis factor-alpha (TNF-α) was the only cytokine showing significantly higher concentration in older athletes, regardless of sport intensity. Interleukin (IL)-10 increased significantly in HI regardless of age group, whereas IL-6 concentration was higher in the older HI athletes. IL-8 showed a significant interaction with sport intensity in different age groups. Overall, significant positive correlations among levels of IL-6, IL-10, IL-8 and TNF-α were identified. The antioxidant catalase activity was positively correlated with levels of TNF-α. Telomere length increased significantly with sport intensity, especially in the younger group. Conclusion: HI had longer telomeres and higher levels of pro- and anti-inflammatory cytokines, suggesting less aging in HI compared to low and moderate counterparts in association with heightened immune response. Investigation of the functional significance of these associations on the health and performance of elite athletes is warranted.

scholarly journals Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3697
Author(s):  
Tae-Kyeong Lee ◽  
Bora Kim ◽  
Dae Won Kim ◽  
Ji Hyeon Ahn ◽  
Hyejin Sim ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hair Growth ◽  
Hair Follicles ◽  
Control Group ◽  
Root Extract ◽  
Dorsal Skin ◽  
Angelica Gigas ◽  
Angelica Gigas Nakai ◽  
Tnf Α ◽  
Anti Inflammatory

This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1β as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1β in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.

scholarly journals Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Financial Burden ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Inflammatory Reactions ◽  
Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

The content of cytokines IL-6, IL-8, TNF-α, IL-4 and the level of expression in macrophages CD86 and CD163 in peritoneal fluid has a reverse correlation with the degree of severity of external genital endometriosis

2019 ◽  
Vol 65 (5) ◽  
pp. 432-436
Author(s):  
A.M. Krasnyi ◽  
A.A. Sadekova ◽  
T.G. Sefihanov ◽  
V.V. Vtorushina ◽  
E.G. Krechetova ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Peritoneal Fluid ◽  
Inflammatory Marker ◽  
Inflammatory Activity ◽  
Control Group ◽  
Reverse Correlation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Degree Of Severity

Concentrations of eight different cytokines and the level of expression of CD86 and CD163 macrophages were studied in peritoneal fluid in women with endometriosis. It was found that the concentration of both inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-4) as well as the level of macrophage expression of the proinflammatory marker CD86 and anti-inflammatory marker CD163 increased in women with mild external genital endometriosis (1-2 stage), and did not differ from the control group in women with severe endometriosis (3-4 stage). The content of IL-2, IL-10, CM-CSF and IFN-γ in the peritoneal fluid of women with endometriosis did not differ significantly from the control group. The results of the study indicate that the development of external genital endometriosis may be based on insufficient both inflammatory and anti-inflammatory activity of macrophages in the peritoneal fluid.

scholarly journals Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

2013 ◽  
Vol 81 (11) ◽  
pp. 4001-4012 ◽  
Author(s):  
Mónica González-Pérez ◽  
Leonardo Mariño-Ramírez ◽  
Carlos Alberto Parra-López ◽  
Martha Isabel Murcia ◽  
Brenda Marquina ◽  
...  
Keyword(s):  
Immune Response ◽  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Mycobacterium Avium ◽  
High Expression ◽  
High Dose ◽  
Content Type ◽  
Subcutaneous Infection ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACTThe genusMycobacteriumcomprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies withMycobacterium tuberculosis. The biological differentiation betweenM. tuberculosisand nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not.Mycobacterium aviumcomplex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after theM. tuberculosiscomplex. Here, we evaluated the virulence and immune response ofM. aviumsubsp.aviumandMycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

Ivig Negatively Regulates LPS-Induced Monocytes Activation Through a Microrna-146a Related Mechanism

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3274-3274
Author(s):  
Lionel Loubaki ◽  
Renée Bazin
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Small Rna ◽  
Cytokine Production ◽  
Innate Immune ◽  
Human Monocytes ◽  
Monocytic Cells ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Stimulation Of

Abstract Abstract 3274 Background: Cells from the monocytic lineage are known to play a central role in the immune defense against pathogens. In the adaptive immune response, they act as antigen presenting cells to trigger T and B cell responses. Monocytic cells also participate in innate immunity following recognition of pathogen-associated molecular patterns (PAMPs) such as bacterial lipopolysaccharides (LPS), which leads to their activation and release of very potent inflammatory mediators. The innate immune response thus needs to be tightly regulated to control not only its onset, but also its termination in order to avoid excessive inflammation. Recent studies have shown that the differentiation and functions of monocytic cells involve small RNA species, named microRNAs (miRNAs). MiRNAs are 21–23 nucleotide long single strand RNAs, which mainly cause gene silencing by degradation of target mRNAs or by inhibition of translation. Among them, miR-146a has captivated interest as it plays an important role in the negative regulation of acute inflammatory responses during activation of the innate immune system. In fact, it has been shown that miR-146a expression is gradually increased in THP-1 monocytic cells following stimulation with LPS or cytokines (e.g. IL-1β and TNF-α) via a NF-κB dependent pathway. MiR-146a inhibits the expression of IRAK1 and TRAF6 leading to the subsequent suppression of NF-κB activity. Consequently, the expression of NF-κB target genes such as IL-1β, TNF-α and PU.1 is suppressed. Therefore, miR146a controls NF-κB signaling via a negative feedback regulation loop and thus can be considered as an anti-inflammatory mediator. IVIg is a therapeutic preparation of polyclonal human IgG isolated from the plasma of thousands of healthy donors. IVIg is well known for its anti-inflammatory effects on a variety of immune cells and processes. More precisely, it has been shown to abrogate the capacity of monocyte-derived dendritic cells to secrete pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines such as IL-10. We thus hypothesize that at least some of the anti-inflammatory effects of IVIg on monocytic cells could be triggered through the modulation of miR-146a expression. Objectives: To evaluate the involvement of miR-146a in the anti-inflammatory effects of IVIg following LPS stimulation of human monocytes. Methods: Human monocytes were obtained from the blood of healthy volunteers and treated with LPS (1 mg/mL) or IVIg (15 mg/mL) alone or alternatively, pretreated with LPS followed by addition of IVIg. Pre-treatment with LPS was done during for 4 h prior to addition of IVIg for 3, 6, 12 and 24 hours. Cells were then recovered and separated in two parts. The first part was used to extract the small RNA fraction of total RNA for miRNA analysis and the second part was used for protein isolation. The miR-146a level was measured by real time PCR while NF-kB and IRF4 protein levels were evaluated by western blotting. Finally, the expression of the transcription factor PU.1 was evaluated by flow cytometry. Results: Our preliminary data revealed that addition of IVIg to LPS-pretreated human monocytes resulted in a significant upregulation of miR-146a expression associated with a significant reduction in NF-κB expression. Furthermore, the expression of the PU.1/IRF4 transcriptional activator complex involved in the stimulation of inflammatory cytokine production was modulated. Indeed, we found that the expression PU.1 was reduced in IVIg-treated cells whereas IRF4 expression was increased, thus promoting the IRF4-mediated cytokine production inhibitory pathway. Conclusion: Our preliminary data suggest that in human monocytes, the anti-inflammatory effects of IVIg may involve miR-146a negative feedback loop regulation of NF-κB activity. Disclosures: No relevant conflicts of interest to declare.

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