Addition of MCP-1 and MIP-3β to the IL-8 appraisal in peritoneal fluid enhances the probability of identifying women with endometriosis (original) (raw)

Peritoneal fluid concentrations of β-chemokines in endometriosis

European Journal of Obstetrics & Gynecology and Reproductive Biology, 2013

Endometriosis, defined by the presence of viable endometrial tissue outside the uterine cavity, is a common chronic inflammatory disease affecting 3-10% of women of reproductive age, and is associated with chronic pelvic pain and infertility. It is an enigmatic disease with unknown etiology and poorly understood pathogenesis. According to the most widely accepted theory, the pathogenesis of endometriosis is a consequence of the implantation of viable endometrial tissues in the pelvis via retrograde menstruation [1]. Although retrograde menstruation is a nearly universal phenomenon among cycling women, only in a subgroup of women will endometrial tissue implant and grow in the peritoneal cavity [2-5]. There is general agreement that endometriosis is a pelvic inflammatory process with altered function of immune-related cells in the peritoneal environment [6]. In particular, macrophages represent the predominant cells in the peritoneal fluid and could play an important role in the development of endometriosis. Immunological dysfunction observed in women with endometriosis may be either a causative agent or simply a result of the disease [7]. These immunological abnormalities may also be implicated in the clinical presentation of the disease, including infertility. The disease is associated with infertility: in addition to obstruction of fallopian tubes due to adhesions, chemokines produced by macrophages and endometriotic tissues induce other factors that negatively affect both sperm motility and embryo implantation [1,5,8]. Women with infertility suffer from endometriosis at a rate of 30-50% [9,10]. According to the American Society of Reproductive Medicine the

Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: relationship to stage of disease

Human Reproduction, 1998

There is increasing evidence that immunological mechanisms play a role in the pathogenesis and pathophysiology of endometriosis. It was therefore of interest to study interleukin-8 (IL-8), a chemokine, in the peritoneal fluid and peripheral blood of women undergoing laparoscopic procedures. The presence and concentrations of IL-8 in relation to endometriosis, infertility and abdominal pain were evaluated. Samples of peritoneal fluid (n ⍧ 49) and peripheral blood (n ⍧ 50) were obtained from 50 consecutive patients undergoing laparoscopic surgery for various gynaecological indications (abdominal pain, infertility, sterilization). IL-8 was present in the peritoneal fluid of most women (87%). The concentration of IL-8 in the peritoneal fluid was higher in women with endometriosis compared to women without (P ϭ 0.02). This difference was more pronounced in early (stage 1) endometriosis (P ⍧ 0.001). IL-8 concentrations in the peritoneal fluid were also higher in women with early endometriosis compared to women with later stages of the disease (P ⍧ 0.003). Peripheral blood concentrations did not correlate with peritoneal fluid concentrations of IL-8 and/or the presence of endometriosis. We conclude that IL-8 is an important factor that may contribute to the pathogenesis of endometriosis possibly by promoting neovascularization. This information can be a guide in the development of new therapeutic approaches for the treatment of endometriosis.

Peritoneal fluid concentrations of interleukin-8 in patients with endometriosis depend on the severity of the disorder and are higher in the luteal phase

Human Reproduction, 2003

BACKGROUND: Previous evaluations of the relationship between the concentrations of interleukin-8 (IL-8) in the peritoneal¯uid and endometriosis led to non-consistent results. Our purpose was to investigate the correlation of the concentrations of IL-8 in the peritoneal¯uid with the stage of endometriosis, the presence of red lesions and the phase of the menstrual cycle. METHODS: Ninety-two patients with infertility (n = 87) or undergoing sterilization (n = 5) had peritoneal¯uid samples collected at laparoscopy. IL-8 determinations were performed using an enzymelinked immunosorbent assay. RESULTS: The concentrations of IL-8 in the peritoneal¯uid of the 68 women with endometriosis were not signi®cantly different from those of the 24 controls. Patients with moderate/severe stages had IL-8 signi®cantly higher than controls (P = 0.008) and marginally higher than patients with minimal/mild endometriosis (P = 0.053). Concentrations of IL-8 were signi®cantly higher in patients than in controls in the luteal phase. Red lesions were associated with signi®cantly increased levels of peritoneal¯uid IL-8 only in the luteal phase. CONCLUSIONS: Our ®ndings reinforce the importance of IL-8 in the pathogenesis of endometriosis.

Peritoneal fluid cytokines related to endometriosis in patients evaluated for infertility

Fertility and sterility, 2017

Our aim was to characterize peritoneal cytokine profiles in patients with infertility, with and without endometriosis, to illuminate potential differences in immune profiles that may reflect mechanistic differences between these two patient populations. Cross-sectional study. University hospital and research center. Women undergoing laparoscopy for infertility investigation (n = 107). Peritoneal fluid was collected during surgery. Clinical characteristics were registered preoperatively. We determined the concentration of 48 different cytokines from the peritoneal fluid with multiplex immunoassays. Associations between cytokines and clinical findings were assessed with logistic regression and partial least squares discriminant analyses (PLS-DA). Concentrations of SCGF-β, IL-8, HGF, and MCP-1 were significantly higher, while IL-13 was significantly lower in the endometriosis group compared with the group without endometriosis. Multiple stepwise logistic regression identified a combina...

Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis

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.

Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial

Fertility and Sterility, 2002

BACKGROUND: The objective of this prospective controlled trial was to investigate the ability of a group of serum and peritoneal fluid (PF) markers to predict, non-surgically, endometriosis. METHODS AND RESULTS: Serum and PF samples were obtained from 130 women while undergoing laparoscopy for pain, infertility, tubal ligation or sterilization reversal. Concentrations of six cytokines [interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-13 and tumour necrosis factor (TNF)-α] were measured in serum and PF, and reactive oxygen species (ROS) in PF, and levels were compared among women who were allocated to groups according to their post-surgical diagnosis. Fifty-six patients were diagnosed with endometriosis, eight with idiopathic infertility, 27 underwent tubal ligation or reanastomosis (control group) and 39 were excluded due to bloody PF. Only serum IL-6 and PF TNF-α could be used to discriminate between patients with and without endometriosis with a high degree of sensitivity and specificity (P < 0.001). A threshold of 15 pg/ml PF TNF-α provided 100% sensitivity and 89% specificity (positive likelihood ratio of 9.1 and negative likelihood ratio of 0). A threshold of 2 pg/ml for serum IL-6 provided a sensitivity of 90% and specificity of 67% (positive likelihood ratio of 2.7 and negative likelihood ratio of 0.14). CONCLUSIONS: By measuring serum IL-6 and PF TNF-α, it was possible to discriminate between patients with endometriosis and those without. Before these markers can be used as a non-surgical diagnostic tool, these data should be verified in a larger study.

Expression of interleukin-8 and monocyte chemotactic protein 1 in women with endometriosis

Fertility and Sterility, 2009

Objective: To investigate the expression and localization of interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in women with and without endometriosis. Design: Comparative immunohistochemical study. Setting: Academic medical center. Patient(s): Ectopic (n ¼ 24) and homologous eutopic endometrium (n ¼ 24) from women with endometriosis and endometrium from women without endometriosis (n ¼ 27) were used for immunohistochemical analysis of IL-8 and MCP-1. Intervention(s): Tissue sections were immunostained with antihuman IL-8 and MCP-1 antibodies. Main Outcome Measure(s): Microscopic evaluation to assess the presence and localization of IL-8 and MCP-1 throughout the menstrual cycle in both eutopic endometrial and endometriotic tissues of women with endometriosis and comparison with normal endometrium. Result(s): In normal endometrium, secretory phase samples expressed higher levels of epithelial IL-8 than in proliferative phase samples. Epithelial MCP-1 expression was similar in both proliferative and secretory phases. Proliferative phase samples showed higher epithelial IL-8 and MCP-1 expressions in eutopic endometrium of women with endometriosis compared with that of normal women. Immunoreactivities of both chemokines were significantly increased in the epithelial cells of ectopic endometrial tissues compared with those of normal endometrium. Conclusion(s): These findings suggest that IL-8 and MCP-1 may be involved in the pathogenesis of endometriosis.

The Peritoneal Fluid Levels of Interleukin-12 in Women with Endometriosis

American Journal of Reproductive Immunology, 1998

Munksgaard, Copenhagen PROBLEM: Interleukin-I2 (IL-I 2) is produced mainly by monocytes/macrophages, and it induces proliferation and cytotoxicity of T-cells and natural killer cells. In women with endometriosis, natural killer cell activity in the peritoneal fluid is significantly decreased. We aimed to measure the peritoneal fluid level of IL-12 in endometriosis. METHOD OF STUDY:We measured IL-12 levels in peritoneal fluid samples from women with or without endometriosis and in supernatants from endometrial stromal, ovarian stromal, and mesothelial cell cultures, using a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: The median concentration of IL-12 in the peritoneal fluid of women with endometriosis was 1.1 pg/ml (range, 0.2-5.5) and was 1.6 pg/ml (range, 0.4-2.8) in women without endometriosis, not a statistically significant difference. IL-12 was not detected in the supernatants of endometrial stromal, ovarian stromal, and mesothelial cell cultures. CONCLUSION: Concentrations of IL-12 in the peritoneal fluid of women with or without endometriosis are low, but they are detectable and are not affected significantly by the presence of endometriosis.

Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis

Fertility and Sterility, 2005

Objective: To investigate the role of interleukin (IL)-16 in peritoneal fluid in the pathogenesis of endometriosis. Design: Comparative and laboratory study. Setting: University of Tokyo Hospital. Patient(s): Peritoneal fluids (PFs) were collected from women without endometriosis (n ϭ 34) and with endometriosis (stages I/II, n ϭ 30; stages III/IV, n ϭ 58). Peritoneal fluid mononuclear cells (PFMCs) were collected from six women. Intervention(s): The PFs were collected; PFMCs were isolated and cultured with or without recombinant human (rh) IL-16. Main Outcome Measure(s): Concentrations of IL-16 in PFs were measured by enzyme-linked immunosorbent assay (ELISA). Concentrations of IL-6, tumor necrosis factor-alpha (TNF-␣), and IL-1␤ in culture media of PFMCs were determined by ELISA.