Journal of Reproductive Immunology 114 (2016) 6–9 Contents lists available at ScienceDirect Journal of Reproductive Immunology jou rn al hom ep age: www.elsevier.com/locate/jreprimm Increased IL-25 levels in the peritoneal fluid of patients with endometriosis Helle Folge Bungum a,∗,1 , Uffe Nygaard b,c,1 , Christian Vestergaard b , Pia M. Martensen d , Ulla Breth Knudsen a a Department of Gynaecology and Obstetrics, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark b Department of Dermatology, Aarhus University Hospital, P.P.Ørumsgade 11, 8000 Aarhus C, Denmark c Department of Clinical medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200 Aarhus N, Denmark d Department of Molecular Biology and Genetics, Aarhus University, C.F. Møllers Allé, 8000 Aarhus C, Denmark a r t i c l e i n f o Article history: Received 16 October 2015 Received in revised form 1 January 2016 Accepted 19 January 2016 Keywords: Endometriosis Type 1 allergy Inflammatory response IL-2 Diagnostic tool Peritoneal fluid a b s t r a c t Previous studies have indicated a higher prevalence of allergic disease among women with endometriosis. It is already well established that type 1 allergies develop in a Th2 cytokine environment. Recent studies have shown, however, that IL-25 induces a Th2 development of naive T lymphocytes and is central in the Th2 response. The aim of this case-control study was to investigate the presence of IL-25 in the peritoneal fluid of women suffering from endometriosis. PF was obtained both from women undergoing laparoscopic surgery due to endometriosis (25 cases) and from women wanting sterilisation (19 controls). IL-25 levels were then investigated by ELISA. Women with endometriosis showed significantly higher levels of IL-25 in their PF (p = 0.019) compared to controls. IL-25 levels did not correlate with the stage of endometriosis. Both Th2-cells and mast cells express IL-25, which could favor the development of allergies by perpet- uating a hypersensitivity reaction. Further, IL-25 may also hold a role as a diagnostic tool. © 2016 Published by Elsevier Ireland Ltd. 1. Introduction Endometriosis is defined by the presence of endometrium-like tissue outside the uterine cavity (Burney and Giudice 2012). Affect- ing up to 10% of women in their reproductive years, it has extensive impact on the affected womens’ work and social life (Simoens et al., 2012) and is a major cause of hospitalization in developed coun- tries. It is widely accepted that the immune system plays a crucial role in the pathogenesis of endometriosis. Considerable research have reported on changes in the peritoneal microenvironment, where defect or altered functions of peritoneal immune cells allows endometriotic lesions to develop and aggravate (Lagana et al., 2013). Further, up- and down-regulation of genes involved in decid- ualization and implantation, seems to be a contributing factor to the inflammatory environment seen in the chronic pelvic inflammation of endometriosis (Kobayashi et al., 2014). ∗ Corresponding author. E-mail address: hellbung@rm.dk (H.F. Bungum). 1 Joint first authorship. (Hsu et al., 1997; Antsiferova et al., 2005) describe increased expression levels of IL-4 in peripheral blood cells, in cells in the ectopic endometrium, and in the peritoneal fluid (PF), as well as ele- vated serum levels, in women with endometriosis. (Gazvani et al., 2001) however found no difference in IL-4 levels Furthermore, several other pro-inflammatory cytokines like IL-17, IL-6, IL-10, TNF  and growth factors have been found in the PF of women with endometriosis, supporting the theory that an inflammatory response plays a crucial part in the pathogenesis of endometriosis (Harada et al., 2001). Recently, we performed a review of the literature concerning the association between endometriosis and allergic disease, but due to poor quality of studies and lack of definitions of allergic disease, no firm conclusions could be made (Bungum et al., 2014). A trend toward a correlation between the two diseases, however, seems to exist. Type 1 allergies develop in a Th2 cytokine environment under the influence of IL-4, –6 and −10. The cytokine IL-25 (also called IL- 17E) has drawn considerable attention in the search for cytokines central to the development and maintenance of the Th2 response, since it induces a Th2 development of naive T lymphocytes (Fort et al., 2001; Ikeda et al., 2003). IL-25 is expressed by Th2-cells and http://dx.doi.org/10.1016/j.jri.2016.01.003 0165-0378/© 2016 Published by Elsevier Ireland Ltd.