scholarly journals RELATION OF Th1, Th2, Treg, Th17 CYTOKINES OF PERITONEAL FLUID IN WOMEN WITH ENDOMETRIOSIS, ASSOCIATED WITH INFERTILITY

Author(s):  
H.D. Koval ◽  
O.M. Yuzko ◽  
A.I. Kurchenko

Endometriosis is one of the leading diseases of the female reproductive organs and is the cause of almost a third of all cases of female infertility. It has been suggested that in women with endometriosis associated with infertility, the levels, nature of production and the ratio of cytokines of cells of different profiles in the peritoneal fluid change, which may play a pathogenetic role (to promote the development of immune inflammation of a certain type) in the development of the disease itself infertility. Aim of the study: to determine the features of the ratio of Th1, Th2, Treg, Th17 cytokines of peritoneal fluid in women with endometriosis associated with infertility. Materials and methods: The study group included 58 women who were diagnosed with external genital endometriosis, namely: peritoneal form and infertility for at least 2 years. The control group consisted of 30 women with tubal genital infertility. No other pathological process, at the time of observation, was detected in control patients. The study was conducted at the Center for Infertility Treatment (Chernivtsi) from 2009 to 2015, following the concept of informed consent of the patient to conduct research and other ethical principles in relation to persons who are the object of the study. Peritoneal fluid was collected during laparoscopy during the proliferative phase of the menstrual cycle. Cytokine levels were determined by enzyme-linked immunosorbent assay (ELISA). The results of the study. The cytokine profile in the peritoneal fluid of women with infertility-associated endometriosis is characterized by an increase in levels of IL-2, TNF-α, IL-6, IL-17, IL-10, IL-18. The largest proportion of all cytokines under study in the peritoneal fluid is IL-10 (28%), followed by IL-2, IL-6 and IL-18 in the order of decreasing relative amount (16%, 14% and 13%, respectively). respectively. The TGF-β (7%) was then placed in relative weight reduction. TNF-α and IL-17 6% each; IL-12 (4%); IL-1β and INF-γ are 3% percent each. The lowest proportion, as in the peripheral blood, was IL-4, which was incomplete 1 percent. The total relative number of cytokines Th1 is 25%, cytokines Th2 – incomplete 15%, cytokines Treg cells – 35%, cytokines Th 17 – IL-17 is 6% and cytokines produced mainly by macrophages and killer cells – 20%. Thus, the total ratio of Th1/Th2 cytokines in women with endometriosis was 2.5:1.5. Conclusions: In the peritoneal fluid, pronounced changes in the cytokine profile are observed, significantly prevail over changes in the peripheral blood, and are characterized by the growth of IL-2 (p <0.001), TNF-α (p <0.001), INF-γ (p <0.001), IL -6 (p <0.001), IL-17 (p <0.001), IL-10 (p <0.001), TGF-β (p <0.05), IL-12 (p <0.001), IL-18 (p <0.001). Local production is characterized by a 2.45-fold decrease in the Th1/Th2 cytokine ratio, which indicates a predominance of the Th2-mediated immune response.

2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


2019 ◽  
Vol 33 ◽  
pp. 205873841982889
Author(s):  
Jiajing Luo ◽  
Yi Chen ◽  
Chengjia Ding ◽  
Jialing Qiu ◽  
Yulan Chen ◽  
...  

The purpose of this study was to focus on the underlying relationship between the hyperactivity for the peripheral monocytes and heat stroke by investigating the inflammatory oxidative activity of and the expression of superficial molecules. Peripheral blood samples were collected from 10 healthy adult volunteers. Human blood monocytes were isolated by density gradient centrifugation and sequent adherent culture. The objectives were divided into four groups: 43°C heat stress combined with lipopolysaccharide (LPS) group, 43°C heat stress group, LPS group, and control group. There were 10 cases in each group. An enzyme-linked immunosorbent assay (ELISA) test was used to measure the concentrations of supernatant inflammatory mediators (tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-10 (IL-10)). After loaded by 2,7-Dichlorodi-hydrofluorescein-diacetate (DCFHDA) fluorescent probe, intracellular reactive oxygen species (ROS) levels were determined by a flow cytometry. After fluorescent microspheres incubation, the phagocytosis of monocytes was observed under a fluorescent microscope. Respectively, the flow cytometry and Western blot were used to evaluate the level of triggering receptor expressed on myeloid cells-1 (TREM-1) and Toll-like receptor-4 (TLR-4) on the monocytes. Furthermore, the mRNA expression of TREM-1 and TLR-4 was detected by real-time polymerase chain reaction (RT-PCR). The heat stress combined with LPS stimulation promoted the peripheral monocytes to produce inflammatory mediators (TNF-α, IL-1β, and IL-10) and release ROS. Otherwise, such complex strike significantly suppressed the phagocytic activity of monocytes in peripheral blood. Moreover, the expression of TREM-1, TLR-4 and CD86 was measured by the flow cytometry on peripheral monocytes which were respectively promoted by the union of heat stress and LPS. The results of Western blot and RT-PCR demonstrated the similar kinetics on these superficial molecules (TREM-1, TLR-4, and CD86) stimulated by the combination of heat stress and LPS. The underlying mechanism of the dysfunction for the peripheral monocytes may be related to the abnormal expression of superficial molecules TREM-1, TLR-4, and CD86 on the monocytes induced by heat stress and LPS.


Author(s):  
L. O. Kuyun

Introduction.    Among surgical diseases, peritonitis is a life-threatening pathological condition characterized by inflammation at both local and systemic levels [8]. Identifying proinflammatory mediators in peripheral blood and in peritoneal fluid and their quantitative characteristic is vital for the diagnosis. High levels of these mediators may be indicators of complications development or lethal outcome. The aim of the study – to learn the levels of proinflammatory and suppressive cytokines in the peripheral blood and compare their properties in patients with acute phlegmonous appendicitis, which causes peritonitis. Materials and Methods. The study measured levels of proinflammatory and suppressive cytokines in the peripheral blood and compare their properties in patients with acute phlegmonous appendicitis, which causes peritonitis. Blood samples from 90 patients with peritonitis and 98 healthy volunteers were analyzed. Blood cytokine content was determined using enzyme-linked immunosorbent assay (Vector-Best). Optical density was measured on an analyzer “Stat FAX 303 PLUS” (USA, pg/ml). The results of the study were statistically analyzed using parametrical and nonparametrical criteria using “Minitab 16” software. Colmogorov-Smirnov test was used to determine the differences between the group of patients and the control group. Key numerical data was gathered and compared using the U-criteria of Mann-Whitney, whereas the average of the two independent data sets were analyzed using the Student method. All persons who took part in the study gave their written consent as required by the bioethics committee. Results and Discussion. The research demonstrated that acute inflammation during phlegmonous peritonitis is characterized by mediator synergy between proinflammatory and suppressive potentials of the immune response at the systemic level. Significant (р<0.001) increase in the levels of proinflammatory (IL-1β, IL-6, TNF-α) and suppressive (IL-10, TGF-β) cytokines in the peripheral blood was observed in patients with phlegmonous peritonitis. Conclusion. Acute inflammation during phlegmonous peritonitis is characterized by mediator synergy between proinflammatory and suppressive potentials of the immune response at the systemic level. Moreover, significant (р<0.001) increase in the levels of proinflammatory (IL-1β, IL-6, TNF-α) and suppressive (IL-10, TGF-β) cytokines in the peripheral blood was observed in patients with phlegmonous peritonitis.


2021 ◽  
Vol 55 (4) ◽  
pp. 217-222
Author(s):  
L.M. Mosiychuk ◽  
O.M. Tatarchuk ◽  
O.P. Petishko

Background. Сhronic atrophic gastritis certainly remains an urgent problem of gastroenterology but data on sexual differences in the content of cytokines in this pathology are quite contradictory. The purpose of the study: to assess the gender chara­cteristics of the cytokine profile in patients with chronic atrophic gastritis. Materials and methods. The study included 120 patients with gastric atrophy, according to histological examination of biop­sies. The control group consisted of 20 healthy individuals, men and women equally. In all patients, we have evaluated the levels of interleukins (IL-8, IL-10, IL-18), tumor necrosis factor alpha (TNF-α), vasculoendothelial growth factor (VEGF) by enzyme-linked immunosorbent assay using appropriate reagent from Vector-BEST kits and the Stat Fax 303 Plus analyzer. Results. In men with chronic atrophic gastritis, there is a more pronounced imba­lance towards pro-inflammatory cytokines, in particular the level of IL-18 is 1.7 times higher (p < 0.05) than in women. In 46.2 % of cases, the content of IL-8 was also elevated in men by 1.3 times (p > 0.05) compared to women. The level of anti-inflammatory cytokine IL-10 does not have a significant gender difference in patients with precancerous conditions of the stomach. The median of IL-18/IL-10 ratio in men is 2 times higher than in women: 65.36 (21.67; 154.25) vs. 32.15 (12.76; 191.85) (p < 0. 05). In males, IL-8/IL-10 ratio is also 1.5 times higher, which is 2.25 (1.29; 7.68) vs. 1.49 (0.75; 9.78) but this difference was not statically significant. Serum content of VEGF in men exceeded the same indicator in women by 1.4 times (p < 0.05). Direct correlation between VEGF content and the levels of TNF-α (r = 0.47, p < 0.05), IL-8 (r = 0.42, p < 0.05), IL-18 (r = 0.58, p < 0.05) confirm the evidence of increased VEGF expression under the influence of many proangiogenic growth factors and proinflammatory cytokines. Conclusions. With an increase in the level of IL-18 and VEGF by more than 30 %, men require dynamic monitoring for early detection of precancerous structural changes in the gastric mucosa.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jiacong Yan ◽  
Chengbo Liu ◽  
Han Zhao ◽  
Chunyan Wang ◽  
Huimei Yao ◽  
...  

Abstract Background This cross-sectional study aimed to evaluate the levels of tumor necrosis factor-alpha (TNF-ɑ), interleukin-8 (IL-8), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-β1) in patients with primary and secondary tubal factor infertility (TFI) compared with fertile subjects, and to compare immune indexes in the serum and peritoneal fluid samples obtained from patients with TFI. Methods The pelvic fluid and peripheral blood of patients with TFI diagnosed by hysteroscopy and laparoscopy were taken as the study objects. The pelvic fluid and peripheral blood of patients who underwent hysteromyomectomy at the same time were taken as the control group. The contents of TNF-ɑ, IL-8, IL-6, and TGF-β1 in serum and peritoneal fluid were determined by enzyme-linked immunosorbent assay, and the levels of these cytokines in serum and pelvic fluid were compared between the two groups. Results Patients with secondary TFI showed significantly higher levels of TNF-ɑ, IL-8, IL-6 and TGF-β1 in the serum (26.15 ± 3.51 vs. 19.61 ± 0.157, 32.18 ± 15.13 vs. 5.73 ± 1.99, 38.84 ± 3.46 vs. 30.48 ± 0.61, and 38.37 ± 3.14 vs. 32.25 ± 1.69, respectively) and peritoneal fluid samples (129.73 ± 183.4 vs. 34.63 ± 0.56, 111.44 ± 207.42 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) compared with the control group. Patients with primary TFI exhibited significantly elevated concentration of TNF-α, IL-8, IL-6 and TGF-β1 in the peritoneal fluid samples (36.88 ± 2.67 vs. 34.63 ± 0.56, 19.47 ± 3.51 vs. 15.34 ± 0.41, 80.01 ± 109.91 vs. 15.67 ± 0.52, and 82.54 ± 115.99 vs. 45.34 ± 0.41, respectively) when compared to the controls. In patients with secondary infertility, the levels of TNF-α (26.15 ± 3.51 vs. 129.73 ± 183.4), IL-8 (32.18 ± 15.13 vs. 111.44 ± 207.42), IL-6 (38.84 ± 3.46 vs. 80.01 ± 109.91) and TGF-β1 (38.37 ± 3.14 vs. 82.54 ± 115.99) in the serum were significantly lower than those in the peritoneal fluid, whereas no significant difference was observed in the primary TFI group between the serum and peritoneal fluid cytokines levels. Conclusion The expression of cytokines in the pelvic environment of patients with TFI is upregulated compared to patients who do not have infertility issues. The detection of cytokines TNF-ɑ, IL-6, IL-8, and TGF-β1 in the pelvic fluid of tubal infertility patients can allow for further understanding of the etiology of TFI.


2021 ◽  
Vol 10 (14) ◽  
pp. 3058
Author(s):  
Aleksandra Mielczarek-Palacz ◽  
Celina Kruszniewska-Rajs ◽  
Marta Smycz-Kubańska ◽  
Jarosław Strzelczyk ◽  
Wojciech Szanecki ◽  
...  

The aim of the analysis was for the first time to assess the expression of genes encoding IL-21 and IL-22 at the mRNA level in ovarian tumor specimens and the concentration of these parameters in serum and peritoneal fluid in patients with ovarian serous cancer. The levels of IL-21 and IL-22 transcripts were evaluated with the use of the real-time RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of proteins. Quantitative analysis of IL-21 gene mRNA in the tumor tissue showed the highest activity in the G1 degree of histopathological differentiation and was higher in G1 compared to the control group. The concentration of IL-21 and IL-22 in the serum and in the peritoneal fluid of women with ovarian cancer varied depending on the degree of histopathological differentiation of the cancer and showed statistical variability compared to controls. The conducted studies have shown that the local and systemic changes in the immune system involving IL-21 and IL-22 indicate the participation of these parameters in the pathogenesis of ovarian cancer, and modulation in the IL-21/IL-22 system may prove useful in the development of new diagnostic and therapeutic strategies used in patients, which require further research.


2021 ◽  
Vol 22 (5) ◽  
pp. 2609
Author(s):  
Guifeng Wang ◽  
Keiichi Hiramoto ◽  
Ning Ma ◽  
Nobuji Yoshikawa ◽  
Shiho Ohnishi ◽  
...  

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups (n = 5, each)—control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks. Plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured using an enzyme-linked immunosorbent assay. The colonic tissue samples were immunohistochemically stained with DNA damage markers (8-nitroguanine and 8-oxo-7,8-dihydro-2′-deoxy-guanosine), inflammatory markers (COX-2 and HMGB1), and stem cell markers (YAP1 and SOX9). The average number of colonic tumors and the levels of IL-6 and TNF-α in the CC + GL group were significantly lower than those in the CC group. The levels of all inflammatory and cancer markers were significantly reduced in the CC + GL group. These results suggest that GL inhibits the inflammatory response by binding HMGB1, thereby inhibiting DNA damage and cancer stem cell proliferation and dedifferentiation. In conclusion, GL significantly attenuates the pathogenesis of AOM/DSS-induced colorectal cancer by inhibiting HMGB1-TLR4-NF-κB signaling.


2018 ◽  
Vol 44 (4) ◽  
pp. 530-538
Author(s):  
Aysun Çetin ◽  
İhsan Çetin ◽  
Semih Yılmaz ◽  
Ahmet Şen ◽  
Göktuğ Savaş ◽  
...  

Abstract Background Limited research is available concerning the relationship between oxidative stress and inflammation parameters, and simultaneously the effects of rosuvastatin on these markers in patients with hypercholesterolemia. We aimed to investigate the connection between cytokines and oxidative stress markers in patients with hypercholesterolemia before and after rosuvastatin treatment. Methods The study consisted of 30 hypercholesterolemic patients diagnosed with routine laboratory tests and 30 healthy participants. The lipid parameters, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), paraoxonase-1 (PON1) and malondialdehyde (MDA) levels in controls and patients with hypercholesterolemia before and after 12-week treatment with rosuvastatin (10 mg/kg/day), were analyzed by means of enzyme-linked immunosorbent assay. Results It was found that a 12-week cure with rosuvastatin resulted in substantial reductions in IL-1β, IL-6 and TNF-α and MDA levels as in rising activities of PON1 in patients with hypercholesterolemia. Before treatment, the PON1 levels were significantly negatively correlated with TNF-α and IL-6 in control group, while it was positively correlated with TNF-α in patients. Conclusion Our outcomes provide evidence of protected effect of rosuvastatin for inflammation and oxidative damage. It will be of great interest to determine whether the correlation between PON1 and cytokines has any phenotypic effect on PON1.


2010 ◽  
Vol 2 ◽  
pp. BIC.S6040 ◽  
Author(s):  
Yulia A. Savitskaya ◽  
Genaro Rico ◽  
Luis Linares ◽  
Roberto González ◽  
René Téllez ◽  
...  

Background Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals ( P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors ( P < 0.001). Conclusions These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.


2021 ◽  
Vol 9 (A) ◽  
pp. 114-118
Author(s):  
Didit Pramudhito ◽  
Suwandi Sugandi ◽  
Ida Parwati ◽  
Muchtan Sujatno ◽  
Soetojo Soetojo

BACKGROUND: Immunological mechanisms of infertility are still poorly understood and controversial, both the cause and treatment. Inflammation, immunology, cell proliferation, cell differentiation, and cell survival are influenced by several proteins, including nuclear factor kappa-B (NFĸB), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). AIM: This study aimed to explore the potential of nano curcumin to prevent anti-sperm antibodies (ASA) formation due to the testes’ inflammatory process in Wistar rats. METHODS: This research is an experimental study with a pre-post-test approach with control group. The research subjects were rats (Rattus norvegicus) of the Wistar strain. The induced animals were grouped into three groups: Group 1 received nano curcumin 1 × 80 mg/kg BW orally, Group 2 received dexamethasone 1 × 0.3 mg/kg BW, and Group 3 received placebo aquadest 1 × 1 mL orally. TNF-α, NF-kB, and IL10 levels in serum were examined with enzyme-linked immunosorbent assay. RESULTS: The nano curcumin treatment showed the ability to reduce the pro-inflammatory cytokine protein TNF-α expression (47.3 ± 2.32) more optimally than dexamethasone treatment (54.4 ± 3.22). Nano curcumin has also shown the ability to reduce the pro-inflammatory cytokine transcription factor, NF-kB (32.5 ± 2.76) more optimally than treatment with dexamethasone (44.6 ± 2.43). CONCLUSION: Nano curcumin can prevent the formation of ASA in testicular trauma through inhibition of the inflammatory response.


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