Peritoneal fluid concentrations of interleukin-11 in women with endometriosis

Objective: To determine the peritoneal fluid concentrations of interleukin-11 (IL-11) in women with endometriosis as compared with the control group.

Design: A prospective, controlled study.

Setting: The obstetrics and gynecology department of a teaching hospital and a university immunology department.

Patient(s): Sixty consecutive women undergoing laparoscopic surgery for benign gynecological indications.

Intervention(s): Peritoneal fluid was obtained during laparoscopy, and the concentration of IL-11 was measured.

Main Outcome Measure(s): Concentration of IL-11 in correlation with the presence of endometriosis, its stage, and the phase of the menstrual cycle.

Result(s): IL-11 was detectable in the peritoneal fluid of 64% of women tested. Concentrations of IL-11 showed no correlation with the presence of endometriosis, the American Fertility Society stage of the disease, or the phase of the menstrual cycle.

Conclusion(s): We found no evidence to suggest that IL-11 is involved in the pathogenesis of pelvic endometriosis.     

Elevated angiogenin levels in the peritoneal fluid of women with endometriosis correlate with the extent of the disorder

OBJECTIVE: To assess the release of angiogenin into peritoneal fluid in women with and without endometriosis by measuring its concentration with reference to disease stage, presence of red lesions, and phase of the menstrual cycle. DESIGN: Retrospective study. SETTING: Nagoya City University Hospital. PATIENT(S): Sixty-four women with endometriosis (n = 38) and cystadenomas (n = 26) for whom surgery was scheduled in the proliferative or secretory phase of the menstrual cycle. INTERVENTION(S): Peritoneal fluid samples were obtained at laparotomy or laparoscopy. MAIN OUTCOME MEASURE(S): Angiogenin concentrations in the peritoneal fluid, as measured by ELISA. RESULT(S): Angiogenin concentration in the peritoneal fluid was markedly elevated in the endometriosis patients (median 515 ng/mL, interquartile range 151-1763 ng/mL) compared with the cystadenoma (control) patients (195 ng/mL, 98-324 ng/mL), with values correlating with the extent of the disease. No significant differences between the proliferative phase and the secretory phase were observed in either the controls or the endometriosis patients. CONCLUSION(S): The inflammation associated with endometriosis, through increasing levels of peritoneal fluid angiogenin, might promote angiogenesis for progression of the disease and correlate with the extent of the disorder.     

Peritoneal fluid concentrations of interleukin-17 correlate with the severity of endometriosis and infertility of this disorder

This prospective study aimed to determine whether patients with endometriosis are having different level of interlukin-17 (IL-17) in peritoneal fluid when compared with patients without endometriosis. The patients with minimal/mild endometriosis had a significantly higher level of IL-17 in peritoneal fluid compared with those with moderate/severe endometriosis or without endometriosis. The concentration of IL-17 in peritoneal fluid was significantly higher when endometriosis and infertility coexist. However, the concentration of IL-17 in peritoneal fluid did not correlate with the phase of the menstrual cycle in the patients with or without endometriosis. Our study suggested that IL-17 might play an important role in the pathogenesis of early endometriosis and endometriosis-associated infertility.     

Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis

OBJECTIVE: To evaluate the presence of macrophage migration inhibitory factor (MIF) in the peritoneal fluid of normal fertile women and patients with endometriosis and its growth-promoting activity toward human endothelial cells. DESIGN: Retrospective study using ELISA to measure peritoneal fluid MIF, and [3H]-thymidine incorporation into the DNA of human endothelial cells to assess its mitogenic activity. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Thirty-six healthy women and 57 women with endometriosis. INTERVENTION(S): Peritoneal fluid samples were obtained at laparoscopy. MAIN OUTCOME MEASURE(S): Macrophage migration inhibitory factor concentrations in the peritoneal fluid samples and [3H]-thymidine incorporation into the DNA of human microvascular endothelial cells to assess proliferation. RESULT(S): This study demonstrated the presence of MIF in the peritoneal fluid and a 238% increase of MIF levels in women with endometriosis as compared with healthy women. Both fertile and infertile women with endometriosis had significantly higher MIF concentrations than did fertile women with normal gynecological status, but the difference was more significant in infertile endometriosis patients. Anti-MIF antibody significantly inhibited proliferation of human microvascular endothelial cells in response to peritoneal fluids from healthy women and women with endometriosis stages I-II and III-IV, as assessed by [3H]-thymidine incorporation. CONCLUSION(S): This study revealed the presence of MIF in the peritoneal fluid and its increased levels in endometriosis and suggests that MIF may be involved in endometriosis-associated infertility and angiogenesis.     

Decreased concentrations of pigment epithelium-derived factor in peritoneal fluid of patients with endometriosis

To determine whether patients with endometriosis have altered levels of pigment epithelium-derived factor (PEDF) in peritoneal fluid, concentrations of PEDF in peritoneal fluid collected from 42 patients with endometriosis and 30 patients without endometriosis were measured with enzyme-linked immunosorbent assay. We detected significantly lower levels of peritoneal fluid PEDF in patients with endometriosis compared with patients without endometriosis, suggesting that peritoneal fluid PEDF plays a role in the pathogenesis of this disorder.     

Elevated glycodelin-A concentrations in serum and peritoneal fluid of women with ovarian endometriosis

Abstract

The aim of this study was to evaluate serum and peritoneal fluid (PF) glycodelin-A concentrations in women with ovarian endometriosis. Ninety-nine matched pairs of serum and PF samples were included in our study. The case group comprised 57 women with ovarian endometriosis and the control group 42 healthy women undergoing sterilization or patients with benign ovarian cysts. Glycodelin-A concentrations were measured using ELISA. Endometriosis patients had significantly higher serum and PF glycodelin-A concentrations compared to controls, and this increase was observed in both proliferative and secretory cycle phases. Glycodelin-A concentrations were more than 10-fold higher in PF than in serum and correlated with each other. Intensity and frequency of menstrual pain positively correlated with glycodelin-A concentrations. Sensitivity and specificity of glycodelin-A as a biomarker for ovarian endometriosis were 82.1% and 78.4% in serum, and 79.7% and 77.5% in PF, respectively. These results indicate that Glycodelin-A has a potential role as a biomarker to be used in combination with other, independent marker molecules.     

NF-κBp65蛋白及ENA-78在子宫内膜异位症发病中的作用研究

目的探讨核因子κBp65(NF-κBp65)蛋白及中性粒细胞活化肽-78(ENA-78)在子宫内膜异位症(内异症)发病中的作用。方法选取2008年10月至2009年2月在山西医科大学第二医院手术切除的卵巢子宫内膜异位囊肿25例,留取异位内膜与在位内膜组织,分为异位内膜组和在位内膜组,选取同期正常的子宫内膜22例为对照组。不同浓度的白细胞介素1β(IL-1β)及IL-1β+二硫氨基甲酸肽吡咯烷(PDTC)分别干预体外传代培养至第3代的在位、异位及正常内膜基质细胞。免疫细胞化学方法及酶联免疫吸附实验(ELISA)检测3组子宫内膜基质细胞NF-κBp65蛋白活化程度及其培养上清液中ENA-78浓度。用IL-1β、IL-1β+PDTC检验各组内膜基质细胞分泌ENA-78及NF-κBp65蛋白的活化程度。结果在位及异位子宫内膜基质细胞培养上清液中ENA-78浓度明显高于正常子宫内膜基质细胞,差异有统计学意义(P0.01);在位及异位子宫内膜基质细胞之间比较,异位子宫内膜基质细胞培养上清液中的ENA-78浓度高于在位子宫内膜基质细胞,差异有统计学意义(P0.01),分别给予IL-1β、IL-1β+PDTC干预后,正常子宫内膜基质细胞上清液中的ENA-78浓度无明显变化(P0.05);而在位及异位内膜基质细胞的上清液中,ENA-78浓度在IL-1β干预后最高,明显高于未干预时及IL-1β+PDTC干预后,差异有统计学意义(P0.01)。3组中,在位及异位内膜基质细胞的NF-κBp65蛋白的活化程度显著高于对照组,差异有统计学意义(P0.05);在位及异位子宫内膜基质细胞NF-κBp65蛋白的活化程度IL-1β干预后最高,显著高于未干预时及IL-1β+PDTC干预后,差异有统计学意义(P0.05)。结论 IL-1β可诱导在位及异位子宫内膜基质细胞NF-κBp65活化,使ENA-78的表达增高。PDTC可抑制此作用,说明NF-κBp65是关键性的调控因子,可能在内异症的发病过程中起到"闸门"的作用,对ENA-78以及其他细胞因子起到重要的调控作用。     

Correlation between symptoms of pain and peritoneal fluid inflammatory cytokine concentrations in endometriosis

Endometriosis affects 10–20% of women during reproductive age and is a common cause of infertility and pain leading to work absenteeism and reduced quality of life.The objective of this study was to investigate the association between the presence and concentration of interleukin-8 (IL-8), RANTES, osteoprotegerin (OPG), pregnancy-associated plasma protein A (PAPP-A), tumour necrosis factor-α (TNF-α), midkine and glycodelin in the peritoneal fluid (PF) and the intensity of pain reported by patients undergoing laparoscopy in our clinic. They rated their pain during menstruation, intercourse and lower abdominal using a visual analogue scale. During laparoscopy, PF was aspirated. Pain scores were correlated to the concentration of the above substances in the PF and to the stage of endometriosis. Endometriosis was histologically confirmed in 41 of 68 participating women; 27 without such evidence were considered as controls. TNF-α and glycodelin correlated positively with the level of menstrual pain. For IL-8, RANTES, OPG and PAPP-A no correlation between their PF concentration and the menstrual pain scores was observed. Patients with severe dysmenorrhoea had increased PF cytokine and marker levels; the difference was significant for TNF-α and glycodelin when compared with the other patients (no or moderate pain). TNF-α and glycodelin may thus play a role in endometriosis and the severity of menstrual pain.     

Peritoneal fluid leptin levels are increased but adiponectin levels are not changed in infertile patients with pelvic endometriosis

Objective.?Endometriosis is a leading cause of infertility, and recent studies suggest that leptin and adiponectin may have a role in its causation and progression. This study assessed levels of leptin and adiponectin in serum and peritoneal fluid (PF) in patients with endometriosis and infertility.

Design and setting.?This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility. Following laparoscopy, patients diagnosed with endometriosis served as cases while patients with no endometriosis served as controls. Patients with polycystic ovarian syndrome, diabetes, thyroiditis and patients on prior therapy with danazol or leuprolide were excluded from the study. Leptin and adiponectin levels were analysed in blood and PF using commercially available ELISA kits.

Results.?Of the 50 patients (aged 22–41 years), 15 had endometriosis (cases) while 35 had no endometriosis (controls). The median PF leptin level was significantly higher in cases as compared to controls (27.7 vs. 15.6?ng/ml, p?=?0.019), and this remained significant even when PF leptin was BMI-normalised (p?=?0.004). However, median serum leptin and adiponectin levels remained comparable between the two groups.

Conclusions.?This study confirmed the role of PF leptin in causation and progression of endometriosis. However, this would have been definitive if healthy fertile females were included in this study.     

Peritoneal fluid concentrations of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and transforming growth factor-beta in women with pelvic adhesions

OBJECTIVE: To establish whether the concentration of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and transforming growth factor-beta (TGF-beta) is influenced by the presence or absence of adhesions, and whether the concentration of these mediators vary throughout the menstrual cycle. DESIGN: Prospective case-control study. SETTING: Women undergoing laparoscopy in a university hospital in the United Kingdom. PATIENT(S): Women undergoing laparoscopy for benign gynecological conditions. INTERVENTION(S): Samples of peritoneal fluid were collected at diagnostic laparoscopy in one group, and at laparoscopy and serially during the first 48 hours after laparoscopic adhesiolysis in a second group. We correlated the concentrations of mediators in serially sampled peritoneal fluid during the 48 hours following laparoscopic adhesiolysis to the adhesion formation and reformation found during second-look laparoscopy. MAIN OUTCOME MEASURE(S): The concentrations of MMP-9, TIMP-1, and TGF-beta in peritoneal fluid. RESULT(S): MMP-9 concentration was lower in the follicular phase than the luteal phase of the menstrual cycle. MMP-9 concentration was significantly lower in women with pelvic adhesions than in women with a normal pelvis. The MMP-9/TIMP-1 ratio is significantly higher in women with significant adhesions at second-look laparoscopy compared to women with minimal or no adhesions. CONCLUSION(S): The components of extracellular matrix remodeling may play an important part in the adhesion formation/reformation process.     

Peritoneal fluid and serum leptin concentrations in women with primary infertility

Aim  Leptin is proposed to participate in the reproductive system of women by acting on either ovaries or hypothalamic-pituitary axis. The objective of the present study is to investigate the leptin concentrations in peritoneal fluid and serum samples of women diagnosed with primary infertility. Methods  A prospective study was carried out in women who underwent laparoscopy within the diagnostic process of primary infertility between January 2005 and January 2007. Leptin concentrations were determined in blood samples obtained before surgery and in peritoneal fluid samples collected during laparoscopy. Results  Peritoneal fluid was obtained from 112 subjects; 21 with unexplained infertility 28 with polycystic ovary syndrome (PCOS), 30 with bilateral tubal occlusion, and 33 with endometriosis. Subjects with PCOS have significantly higher body weights, BMI values and plasma leptin levels when compared to other study groups. Peritoneal fluid levels of leptin were significantly higher in the endometriosis group compared to other three study groups. A positive correlation was found between peritoneal fluid leptin levels and the endometriosis stage (r = 0.51, P = 0.01). However, plasma leptin levels were unrelated to the disease extent. Discussion  It might be hypothesized that leptin may be an active factor in the pathogenesis of PCOS and endometriosis, which are two major causes of primary infertility. A mild leptin deficiency in peritoneal environment may interrupt follicular development and ultimately lead to PCOS. Leptin has angiogenic and mitogenic properties, which trigger inflammatory cytokines and eventually result in the development of endometriosis implants. Significantly, higher levels of leptin in peritoneal environments of endometriosis subjects strongly imply the important role of this common pathology.     

Effect of peritoneal fluid from endometriosis patients on neuroblastoma cells in culture

Aim.?Endometriosis is often associated with lower abdominal pain, dysmenorrhea, dyspareunia, and chronic pelvic pain. There is no correlation between the extent of endometriosis and the intensity of pain. The mechanism of pain in endometriosis is unknown. The aim of our study was to investigate the influence of peritoneal fluid (PF) from endometriosis patients on cultured neural cells that are the morphological basis of nociception, and to determine whether there was a relationship between the rAFS staging and an elevation of TGF-β1 production by these cells.

Methods.?Different human neuroblastoma cell lines were grown to 3/4 confluence and then cultured in presence of PF pooled according to the presence of no, mild, or severe endometriosis. After 6 and 24?h of incubation, the morphological changes were assessed and the metabolic activity was determined.

Results.?The different cell lines showed strongly varying proliferation and aggregation patterns. The metabolic activity was also varying between cell lines, but no consistently increased cell turnover in the PF when compared with the control medium nor associated to a particular, endometriosis-derived PF pool could be shown. In this experimental setting, we have observed that the cell proliferation in the presence of PF was inhibited, and not enhanced as it might have been expected. Measurement of TGF-β1 showed higher production rates for this cytokine under exposure to PF than in controls for some but not all tested cell lines, but there was no association with the stage (rAFS) of the disease.

Conclusion.?The neuronal cell culture model may become a useful tool to investigate the endometriosis-derived pain, but different endpoints and cell lines may have to be introduced.     

Levels of Galectin-3 and Stimulation Expressed Gene 2 in the peritoneal fluid of women with endometriosis: a pilot study

Endometriosis is a puzzling disorder with obscure pathogenesis. Several studies suggest that peritoneal fluid is a key inflammatory environment in the development and progression of the disease. This study analyzed the levels of two inflammatory factors – Galectin-3 and Stimulation Expressed Gene 2 – in the peritoneal fluid of 15 women affected by endometriosis and 8 controls. The peritoneal fluid was collected during laparoscopic surgery avoiding any form of contamination and it was properly processed and stored. Gal-3 and ST2 peritoneal concentrations were analyzed using enzyme immunoassay kit. Gal-3 levels were significantly higher in endometriosis group than in controls (64.7?±?52.34 versus 21.05?±?20.83?ng/ml, p?=?0.044), whereas ST2 concentrations did not differ between the two groups. A significant positive correlation was found between Gal-3 and ST2 levels. Gal-3 levels positively correlated with the stage of endometriosis, the duration of symptoms, Marinoff scale and VAS score, while ST2 levels were positively associated with VAS score. Our results suggest that Gal-3 and ST2 could be implicated in the inflammatory process of the disease. Further studies are needed to identify markers of early diagnosis and to open new therapeutic avenues in endometriosis.