Cytokine and immune cell levels in peritoneal fluid and peripheral blood of women with early- and late-staged endometriosis (original) (raw)
Related papers
Archives of Gynecology and Obstetrics, 2001
In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFβ1), and Interferon-gamma (IFN-γ). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFβ1, IFNγ, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings.
Fertility and Sterility, 2005
Objective: To estimate regulatory cytokine synthesis and lymphocyte activation in the peripheral blood and endometrial tissue of patients with endometriosis. Design: Controlled clinical study. Setting: Medical center. Patient(s): Fifteen women with laparoscopically diagnosed endometriosis; 20 gynecologically healthy women with previously documented fertility (control group). Intervention(s): Peripheral venous blood sampling; laparoscopic collection of ectopic and matched eutopic endometrium. Main Outcome Measure(s): Messenger RNA (mRNA) for interleukin (IL)-2, IL-4, and IL-10 expression in peripheral and endometrium lymphocytes was assessed by real-time reverse transcriptase polymerase chain reaction; intracellular synthesis of these cytokines and lymphocyte phenotype profile were established by flow cytometry. Result(s): Both mRNA expression and intracellular synthesis of IL-4 and IL-10 were sharply increased in peripheral lymphocytes. The same changes were observed for IL-4 in ectopic endometrium of women with endometriosis. Simultaneously, elevation of the amount of pan-B cells, CD20ϩCD5ϩ B-1 cells, and activated HLA-DRϩCD20ϩ B lymphocytes was observed in endometriosis lesions. Only an enhanced amount of B lymphocytes was seen in eutopic endometrium. Conclusion(s): Endometriosis development is accompanied by the activation of a T-helper type 2 immune response at the systemic and local levels. Our results support the hypothesis regarding the autoimmune nature of endometriosis and can explain the high level of autoantibody production in patients with endometriosis.
Potential involvement of the immune system in the development of endometriosis
Reproductive biology and endocrinology : RB&E, 2003
This article presents an overview of immunological factors and their role in the development of endometriosis, with emphasis on inflammatory cytokines, growth and adhesion factors. Although retrograde menstruation is a common phenomenon among women of reproductive age, not all women who have retrograde menstruation develop endometriosis. The development of endometriosis is hypothesised to be a complex process, which may be facilitated by several factors, including the quantity and quality of endometrial cells in peritoneal fluid (PF), increased inflammatory activity in PF, increased endometrial-peritoneal adhesion and angiogenesis, reduced immune surveillance and clearance of endometrial cells, and increased production of autoantibodies against endometrial cells. Potential biomarkers like cytokines and autoantibodies upregulated during development of endometriosis may be useful in the development of a non-surgical diagnostic tool. Although endometriosis can be treated using hormonal...
Serum cytokines as biomarkers for nonsurgical prediction of endometriosis
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2008
Objective: To test the ability of a group of serum cytokines, either individually or in combination, to serve as biomarkers for the nonsurgical diagnosis of endometriosis. Study design: Subjects were allocated to two groups according to their laparoscopic diagnosis. The first group consisted of patients with endometriosis and the second group was made up of infertile women with no pelvic pathology (controls). Blood samples were collected preoperatively and stored. Cytokines were measured in the serum of all participants using the Bio-Plex Protein Array System. Nonparametric statistics and the Mann-Whitney test were used to compare groups. Subjects were seen at the Gynecologic endoscopy unit. Results: Three cytokines were significantly higher in the serum of subjects with endometriosis than in the control group: interleukin-6 (IL-6) [4.41 pg/ml (range: 1.47-15.01) versus 0.97 pg/ml (range: 0.29-2.98), respectively; p < 0.001], monocyte chemotactic protein-1 (MCP-1) [37.91 pg/ml (range: 24.54-94.74) versus 22.13 pg/ml (range: 13.85-39.45), respectively; p < 0.001], and interferon-gamma (INF-g) [19.01 pg/ml (range: 1.19-73.52) versus 0.30 pg/ml (range: 0.00-13.05), respectively; p < 0.001]. There was no statistically significant difference between subjects with endometriosis and controls in the serum concentration of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-a), or granulocyte macrophage colony stimulating factor (GM-CSF). Interleukin-2 (IL-2), interleukin-8 (IL-8), and interleukin-15 (IL-15) were undetectable in the serum of both groups. None of the measured cytokines showed significant correlation with the cycle phase or stage of endometriosis. In a multivariate analysis, serum interleukin-6 provided a sensitivity of 71% and a specificity of 66% to discriminate between endometriosis patients and controls at a cutoff point of 1.9 pg/ml. Adding monocyte chemotactic protein-1 and interferon-gamma to interleukin-6 did not increase the discriminative ability over that achieved by measuring serum interleukin-6 alone. Conclusions: Serum of subjects with endometriosis contains significantly higher levels of interleukin-6, monocyte chemotactic protein-1, and interferon-gamma than control women. Serum interleukin-6 measurements discriminate between women with endometriosis and controls. Interleukin-6 provides a promising serum marker for the nonsurgical prediction of endometriosis. #
Alterations of CD4+T Cell Subsets in Blood and Peritoneal Fluid in Different Stages of Endometriosis
Volume 14, No 3, October-December , 2020
Background: Endometriosis is a chronic inflammatory disorder with known immune disturbances. The aim of this study was to compare the frequency of different CD4+ T cells [T helper (Th)1, Th2, Th17 and regulatory T cells (Tregs)] in peripheral blood (PB) and peritoneal fluid (PF) of patients that have early and advanced stages of endometriosis with a control group. Materials and Methods: In this case control study, PB and PF samples were collected from women aged 24-40 years who underwent laparoscopy procedures. The frequency of CD4+ T subsets were analysed by flow cytometry and compared between three study groups; early endometriosis (stage I, II), advanced endometriosis (stage III, IV) and control (no endometriosis). T cell numbers were compared between the PB and PF in each of the aforementioned groups. Results: No statistically significant difference was found between the study groups regarding the numbers of Th1, Th2 and Th17 cells in PB. The PF of patients with advanced endometriosis had increased numbers of Th17 cells compared to the control group (P=0.003), with P values of 0.059 and 0.045 in both menstrual phases. Increased numbers of Th2 cells in PF from early compared to advanced stages of endometriosis were detected exclusively in the luteal phase (P=0.035). The control group had increased numbers of Treg and Th2 cells in the PF compared to PB (both, P value=0.046). However, in the early stages of endometriosis there were more Th2, Th17 and Treg cells in the PF compared to PB (P values: 0.005, 0.047 and 0.013, respectively), while the number of Th17 cells was higher in the PF compared with PB in the advanced stages of endometriosis (P= 0.013). Conclusion: There were increased numbers of Th17 cells in the PF of patients with advanced stages of endometriosis, which could be related to the severity of this disease.
Central European Journal of Immunology, 2015
The aim of the study was to investigate the serum pro-inflammatory cytokine profile in patients with diagnosed endometriosis. Material and methods: The study included 160 women, who were divided in two study groups (Group I-endometriosis; Group 2-healthy). We evaluated the serum levels of interleukin (IL)-1β, IL-5, IL-6, IL-7, and IL-12, and of tumour necrosis factor α (TNF-α) with the use of Human Multiplex Cytokine Panels. Results: The serum level of IL-1β, IL-6, and TNF-α is significantly higher in women with endometriosis compared to women free of disease, from the control group (mean 10.777, 183.027, and 131.326, respectively, compared to 3.039, 70.043, and 75.285, respectively; p = 0.002, p < 0.001, and p = 0.015, respectively). No significant differences in the serum levels of IL-5 and IL-12 were observed between the studied groups, and IL-7 had a very low detection rate. Conclusions: Women with endometriosis have elevated levels of key pro-inflammatory cytokines, i.e. IL-1β, IL-6, and TNF-α. At the same time, IL-1β and IL-6 could be used as predictors for endometriosis.
Alteration of systemic and uterine endometrial immune populations in patients with endometriosis
American Journal of Reproductive Immunology, 2020
Problem: Endometriosis is defined as growth of endometrial tissue in ectopic locations, it is associated with infertility, chronic pain and affects ~12% of reproductive aged women. Although inflammation is known to play a key role in endometriosis, knowledge related to immune phenotypes associated with this disease is lacking. This study aimed to characterize immune profiles in patients with endometriosis, to assess inflammatory mediators and determine if surgical and/or hormonal therapies restore immune homeostasis. Methods of study: Samples from 9 controls and 20 histologically confirmed endometriosis patients were collected upon surgery and ~1-3 weeks post-surgical intervention. Subjects were either not utilizing hormonal suppression or were currently on monophasic hormonal therapy. Tolerant regulatory T-cells (Tregs = natural [nTregs] + inducible [iTregs]) and inflammatory T-helper 17 (Th17) cells were identified in peripheral blood via flow cytometry and within the eutopic/ectopic endometrial tissues via immunohistochemistry and real-time-qPCR. Cytokines were assessed via 10-plex-ELISA. Results: Patients with endometriosis not utilizing hormonal therapy exhibited lower iTregs (tolerant), greater Th17 (inflammatory) and a reduction in Treg/Th17 ratio (p<0.05), indicative of systemic inflammation. Treg and Th17 localizations were enhanced within the ectopic endometrial implant, which promotes lesion development. Hormonal therapy decreased systemic and local inflammation (eutopic/ectopic endometrium) via decreased iTregs and Th17 cells in patients with endometriosis (p<0.05). Thus, imbalance within immune populations correlated with increased inflammation in patients with endometriosis, which was mitigated by hormonal therapy. Conclusions: Patients with endometriosis exhibited systemic and localized inflammation within ectopic and endometrial tissues. Hormonal therapy dampened inflammation caused by disease.
American Journal of Obstetrics and Gynecology, 1996
OBJECTIVE: The levels of interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-lO, and granulocyte-macmphage colony-stimulating factor were measured in the peritoneal fluid of 15 patients with endometriosis to characterize the type of immune response that occurs at the site of endometriosis. STUDY DESIGN: Cytokine levels in peritoneal fluid obtained during laparoscopy from 15 patients and 12 controls undergoing tubal ligation were determined by enzyme-linked immunosorbent assay. RESULTS: The mean levels of interleukin-6 in patients with enclometriosis and controls were 797 _+ 407 pg/ml and 133 + 38 pg/ml, respectively (p < 0.02). Similarly, the mean concentration of interleukin-10 in peritoneal fluids of patients with endometriosis was significantly higher than that of controls (241 + 38 vs 128 + 21, p < 0.05). The levels of interleukin-2, interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor were not significantly different between the two study groups. CONCLUSIONS: The levels of interleukin-6 and interleukin-10 are increased in the peritoneal fluids of patients with endometriosis, suggesting enhanced macrophage activity in these patients. Increased interleukin-6 and interleukin-10 production may partially contribute to the disturbed immune regulation observed in patients with endometriosis. (AM J OBSTF GYNEOOL 1996;174:1522-6.)