T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

Andreoli, C; Genro, Vanessa Krebs; Souza, Carlos Augusto Bastos de; Michelon, Tatiana; Bilibio, João Paolo; Scheffel, Camila; Cunha-Filho, João Sabino

doi:10.1016/j.fertnstert.2011.02.019

Cited by 57 publications

(36 citation statements)

References 38 publications

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“…In other words, IL-6 enhances the activation of the immune system, perpetuating the inflammatory process. Some present data similar to our own, where no differences were observed [33][34][35] and others showing an elevation in the peritoneal fluid. Kyama et al 23 reached a similar conclusion when IL-6 concentration in peritoneal fluid was significantly higher in patients with endometriosis in comparison with women without the disease, but contrary to our results, it was related to the menstrual cycle, it being higher during the menstrual period.…”

Section: Discussionsupporting

confidence: 91%

“…Kyama et al 23 reached a similar conclusion when IL-6 concentration in peritoneal fluid was significantly higher in patients with endometriosis in comparison with women without the disease, but contrary to our results, it was related to the menstrual cycle, it being higher during the menstrual period. 37 Similar to our study, Andreoli et al 35 did not find any difference in IL-17 peritoneal fluid concentration in patients with or without endometriosis. [24][25][26] TGF-b is profusely expressed in the endometrium and it is related to cell proliferation, differentiation, apoptosis, and tissue remodeling.…”

Section: Discussionsupporting

confidence: 90%

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CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

Podgaec

Rizzo

Fernandes

et al. 2012

American J Rep Immunol

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Problem To evaluate CD4+CD25highFoxp3+ cells and IL‐6, IL‐10, IL‐17, and TGF‐β in the peritoneal fluid of women with endometriosis. Method of study A total of ninety‐eight patients were studied: endometriosis (n = 70) and control (n = 28). First, peritoneal fluid lymphocytes were isolated, and CD4+CD25high cells were identified using flow cytometry. Then, RT‐PCR was performed to verify Foxp3 expression in these cells. Also, IL‐6, IL‐10, IL‐17, and TGF‐β concentration was determined. Results Of all the lymphocytes in the peritoneal fluid of women with endometriosis, 36.5% (median) were CD4+CD25high compared to only 1.15% (median) in the control group (P < 0.001). Foxp3 expression was similarly elevated in patients with the disease compared to those without (median, 50 versus 5; P < 0.001). IL‐6 and TGF‐β were higher in endometriosis group (IL‐6: 327.5 pg/mL versus 195.5 pg/mL; TGF‐β: 340 pg/mL versus 171.5 pg/mL; both P < 0.001). IL‐10 and IL‐17 showed no significant differences between the two groups. Conclusion The peritoneal fluid of patients with endometriosis had a higher percentage of CD4+CD25highFoxp3+ cells and also higher levels of IL‐6 and TGF‐β compared to women without the disease. These findings suggest that CD4+CD25highFoxp3+ cells may play a role in the pathogenesis of endometriosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

Podgaec

Rizzo

Fernandes

et al. 2012

American J Rep Immunol

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“…As anticipated, the macrophage secretion signature collectively ranked very high within this ordering, along with canonical macrophage surface markers such as CD14, CD68, and HLA-A/B/C. Moreover, numerous gene products previously associated with endometriosis in independent studies were observed within the top ten percent of genes in the co-expression profile, including IL-23 (26), soluble TNF receptors I & II (27), MIP-3β/CCL19 (28), ENA-78/CXCL5 (29), MMP-9 (30), CCR1 (31), C3 (32), NFκB (33), and Cox-1/2 (34). To verify that these inferences were not unique to the expression structure present in IRIS, we examined a second co-expression profile derived from the Human Immune Cell Transcriptome (HICT) compendia (35), which demonstrated broad correspondence with IRIS profile rankings ( P < 10 −9 , Spearman correlation) and comparable enrichment of the independently validated inflammatory markers noted above among the top ten percent of proximal co-expression partners.…”

Section: Resultssupporting

confidence: 53%

Molecular Network Analysis of Endometriosis Reveals a Role for c-Jun–Regulated Macrophage Activation

et al. 2014

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Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentations, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify novel approaches to targeted treatment. Here, we employ a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient sub-populations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared “consensus signature” of thirteen elevated cytokines that was associated with common clinical features, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the NFκB family emerged among over-represented transcriptional binding sites for consensus markers, our analysis provides evidence for a previously unrecognized contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses provide in vivo validation of a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of novel agents aimed at curtailing inflammatory mechanisms that drive disease progression.

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“…Conversely, a nested case-control study of adult women with varied symptoms showed higher median peritoneal fluid IL-2 levels in the endometriosis group [9]. Serum levels of IL-10, an anti-inflammatory cytokine, were found increased in some patients with advanced stage endometriosis [5], but this difference was not observed in other studies [32,33], except in a subgroup of patients with ovarian disease [9]. …”

Section: Discussionmentioning

confidence: 97%

Prospective Evaluation of a Panel of Plasma Cytokines and Chemokines as Potential Markers of Pelvic Endometriosis in Symptomatic Women

Rocha

Vieira²,

Maia³

et al. 2016

Gynecol Obstet Invest

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Background: Endometriosis is a chronic inflammatory disease for which no accurate peripheral diagnostic marker is available. Many cytokines and chemokines have been found altered in the plasma and peritoneal fluid of women with endometriosis compared to healthy controls, but little is known about their diagnostic utility to confirm or discard endometriosis among symptomatic women. Objective: The study aims to assess the diagnostic value of a panel of plasma cytokines and chemokines to detect endometriosis in women undergoing laparoscopy for gynecological complains. Methods: We performed a prospective cohort study evaluating simultaneously plasma concentrations of interleukin (IL)-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 in 75 symptomatic women (chronic pelvic pain, infertility or ovarian cyst) submitted to laparoscopy. Assays were performed by Cytometric Bead Array System. Endometriosis was confirmed by histopathological examination of surgical specimens. Results: Plasma IL-2, IL-4, IL-6, IL-10, MCP-1/CCL2, IP-10/CXCL10 and eotaxin/CCL11 concentrations were not able to distinguish the women who eventually were diagnosed with endometriosis. Conclusion: Although previously shown to be altered in women with endometriosis compared to healthy women, the tested cytokines and chemokines were not useful to predict the presence of endometriosis among symptomatic women. This finding suggests that inflammatory markers modified by endometriosis may also be altered by other conditions associated with similar symptoms, which limits their use in clinical practice.

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T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

Cited by 57 publications

References 38 publications

CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

Molecular Network Analysis of Endometriosis Reveals a Role for c-Jun–Regulated Macrophage Activation

Prospective Evaluation of a Panel of Plasma Cytokines and Chemokines as Potential Markers of Pelvic Endometriosis in Symptomatic Women

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T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

Cited by 57 publications

References 38 publications

CD4+CD25highFoxp3+ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

CD4+CD25highFoxp3+ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

Molecular Network Analysis of Endometriosis Reveals a Role for c-Jun–Regulated Macrophage Activation

Prospective Evaluation of a Panel of Plasma Cytokines and Chemokines as Potential Markers of Pelvic Endometriosis in Symptomatic Women

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CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

CD4⁺CD25^highFoxp3⁺ Cells Increased in the Peritoneal Fluid of Patients with Endometriosis