Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis

Abstract

Please cite this paper as: Mier‐Cabrera J, Jiménez‐Zamudio L, García‐Latorre E, Cruz‐Orozco O, Hernández‐Guerrero C. Quantitative and qualitative peritoneal immune profiles, T‐cell apoptosis and oxidative stress‐associated characteristics in women with minimal and mild endometriosis. BJOG 2011;118:6–16. Objectives To assess immunological variables, T‐cell apoptosis and oxidative stress markers in the peripheral blood and peritoneal fluid of women with (WEN) and without (WWE) endometriosis. Design Observational and transverse case–control study. Setting National Institute of Perinatology, Mexico City, Mexico. Population and sample Peripheral blood and peritoneal fluid obtained from 30 WWE and 32 WEN. Methods Blood was drawn before surgery and peritoneal fluid was collected during surgery but before any surgical procedure had been carried out. Flow cytometry, spectrophotometry, high‐performance liquid chromatography and multiplex immunoassay analyses were performed. Main outcome measures Peripheral and peritoneal lymphocyte subpopulations (CD3+, CD4+ CD3+, CD8+ CD3+, CD16+ CD56+, human leucocyte antigen‐DR+ CD3+ and CD19+), intracellular CD4+ CD3+ and CD8+ CD3+ cytokine synthesis (interleukin‐2 [IL‐2] and interferon‐γ [IFN‐γ]), CD3+ apoptosis, malondialdehyde and ascorbate concentrations and peritoneal cytokine concentrations. Results No differences were found in peripheral and peritoneal lymphocyte subsets between the groups. Peritoneal T lymphocytes from WEN produced less IL‐2 and IFN‐γ than those from WWE. Peritoneal malondialdehyde concentrations were higher and ascorbate concentrations were lower in WEN than in WWE. Higher peritoneal concentrations of pro‐inflammatory cytokines (IL‐1β, tumour necrosis factor‐α and IL‐6) and chemokines (IL‐10, IL‐8, eotaxin, vascular endothelial growth factor, monocyte chemotactic protein‐1 and regulated upon activation, normal T‐cell expressed, and secreted) and lower concentrations of IFN‐γ, IL‐1 receptor antagonist and IL‐15 were found in WEN. No statistical differences were found in IL‐2, IL‐4, IL‐12 and IL‐13 concentrations. Conclusion The alterations observed in WEN were associated with a diminished peritoneal T helper type 1 immune response. Pro‐inflammatory, chemotactic, angiogenic and oxidative stress markers were altered in the peritoneal milieu of WEN. These changes appeared to contribute to the peritoneal immune alterations found.

Role of iron overload-induced macrophage apoptosis in the pathogenesis of peritoneal endometriosis

“…Altered immune responses play a prominent role in the development of peritoneal endometriosis due to failure to remove the ectopic endometrial cells (Giudice & Kao 2004, Mier-Cabrera et al 2010. Numerous evidences indicate that the immune cells facilitate the establishment of endometriotic lesion and modulate endometriosis-associated pain and infertility as well (Berbic et al 2009).…”

Serum and peritoneal fluid levels of ischemia modified albumin in moderate/severe endometriosis

“…Up to day numerous papers reported increased levels of different oxidative stress markers in peritoneal fluid of endometriosis cases. 8,12,13,21 The results of this study suggested that OS, detected as elevated IMA levels, may be confined to the peritoneal cavity in women with advanced stage endometriosis. Moreover, this is the first is study in the literature documenting IMA levels in peritoneal fluid of endometriosis cases.…”

“…In endometriosis, peritoneal fluid contains high concentrations of pro-inflammatory and chemotactic cytokines that activates phagocytic cells and apoptotic endometrial tissue accumulated in endometriotic implants, which are the basic producers of ROS. 12 Therefore, in our study peritoneal fluid IMA levels were analysed as well. Up to day numerous papers reported increased levels of different oxidative stress markers in peritoneal fluid of endometriosis cases.…”

“…[6][7][8][9] While some studies failed to observe increased OS in systemic circulation or peritoneal fluid of patients with endometriosis, others have reported increased levels of OS markers in those with the disease. [10][11][12][13] Ischemia-modified albumin (IMA) measured by the albumin cobalt binding test was used originally as a biomarker for evaluating patients with cardiac ischemia. 14 The accurate mechanism of how IMA is produced in presence of ischemia is unclear but appears to be related to the production of ROS that modify the metal binding sites.…”

Oxidative stress in pregnancy and fertility pathologies

“…In several independent studies regarding this pathology and oxidative stress biomarkers, peritoneal fluid from women suffering from endometriosis was found to have increased levels of MDA, 8-OHdG, 8-oxoguanine DNA glycosylase, protein carbonyls, interleukin-6, TNFα, interleukin-1β, interleukin-8, VEGF, and 8-iso-prostangladin F2-alpha (8-iso-PGF2α) (Andrade et al2010;Carvalho et al 2013;Matsuzaki and Schubert2010;Mier-Cabrera et al 2011;Montuschi et al 2004;Morrow et al 1992;Rong et al 2002;Sharma et al2010). Furthermore, 8-iso-PGF2α levels were concluded to be useful in predicting oxidative status in diseases such as endometriosis (Montuschi et al 2004;Morrow et al 1992;Sharma et al 2010).…”