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.

Bulun SE: Endometriosis. N Engl J Med 2009;360:268-279.
Rogers PA, D'Hooghe TM, Fazleabas A, Gargett CE, Giudice LC, Montgomery GW, Rombauts L, Salamonsen LA, Zondervan KT: Priorities for endometriosis research: recommendations from an international consensus workshop. Reprod Sci 2009;16:335-346.
Fassbender A, Vodolazkaia A, Saunders P, Lebovic D, Waelkens E, De Moor B, D'Hooghe T: Biomarkers of endometriosis. Fertil Steril 2013;99:1135-1145.
May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM: Peripheral biomarkers of endometriosis: a systematic review. Hum Reprod Update 2010;16:651-674.
Suen JL, Chang Y, Chiu PR, Hsieh TH, Hsi E, Chen YC, Chen YF, Tsai EM: Serum level of IL-10 is increased in patients with endometriosis, and IL-10 promotes the growth of lesions in a murine model. Am J Pathol 2014;184:464-471.
Kalu E, Sumar N, Giannopoulos T, Patel P, Croucher C, Sherriff E, Bansal A: Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis. J Obstet Gynaecol Res 2007;33:490-495.
Othman Eel-D, Hornung D, Salem HT, Khalifa EA, El-Metwally TH, Al-Hendy A: Serum cytokines as biomarkers for nonsurgical prediction of endometriosis. Eur J Obstet Gynecol Reprod Biol 2008;137:240-246.
Drosdzol-Cop A, Skrzypulec-Plinta V, Stojko R: Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain. Obstet Gynecol Surv 2012;67:374-381.
Podgaec S, Dias Junior JA, Chapron C, Oliveira RM, Baracat EC, Abrao MS: Th1 and Th2 immune responses related to pelvic endometriosis. Rev Assoc Med Bras 2010;56:92-98.
Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C: The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998;70:425-431.
Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A: Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 2002;17:426-431.
Martinez S, Garrido N, Coperias JL, Pardo F, Desco J, Garcia-Velasco JA, Simon C, Pellicer A: Serum interleukin-6 levels are elevated in women with minimal-mild endometriosis. Hum Reprod 2007;22:836-842.
Somigliana E, Vigano P, Tirelli AS, Felicetta I, Torresani E, Vignali M, Di Blasio AM: Use of the concomitant serum dosage of CA 125, CA 19-9 and interleukin-6 to detect the presence of endometriosis. Results from a series of reproductive age women undergoing laparoscopic surgery for benign gynaecological conditions. Hum Reprod 2004;19:1871-1876.
Seeber B, Sammel MD, Fan X, Gerton GL, Shaunik A, Chittams J, Barnhart KT: Panel of markers can accurately predict endometriosis in a subset of patients. Fertil Steril 2008;89:1073-1081.
Jee BC, Suh CS, Kim SH, Moon SY: Serum soluble CD163 and interleukin-6 levels in women with ovarian endometriomas. Gynecol Obstet Invest 2008;66:47-52.
Agic A, Djalali S, Wolfler MM, Halis G, Diedrich K, Hornung D: Combination of CCR1 mRNA, MCP1, and CA125 measurements in peripheral blood as a diagnostic test for endometriosis. Reprod Sci 2008;15:906-911.
Galleri L, Luisi S, Rotondi M, Romagnani P, Cobellis L, Serio M, Petraglia F: Low serum and peritoneal fluid concentration of interferon-gamma-induced protein-10 (CXCL10) in women with endometriosis. Fertil Steril 2009;91:331-334.
Gmyrek GB, Sozanski R, Jerzak M, Chrobak A, Wickiewicz D, Skupnik A, Sieradzka U, Fortuna W, Gabrys M, Chelmonska-Soyta A: Evaluation of monocyte chemotactic protein-1 levels in peripheral blood of infertile women with endometriosis. Eur J Obstet Gynecol Reprod Biol 2005;122:199-205.
Borrelli GM, Abrao MS, Mechsner S: Can chemokines be used as biomarkers for endometriosis? A systematic review. Hum Reprod 2014;29:253-266.
Reis FM, Petraglia F, Taylor RN: Endometriosis: hormone regulation and clinical consequences of chemotaxis and apoptosis. Hum Reprod Update 2013;19:406-418.
Fassbender A, Burney RO, O DF, D'Hooghe T, Giudice L: Update on biomarkers for the detection of endometriosis. Biomed Res Int 2015;2015:130854.
Podgaec S, Abrao MS, Dias JA Jr, Rizzo LV, de Oliveira RM, Baracat EC: Endometriosis: an inflammatory disease with a Th2 immune response component. Hum Reprod 2007;22:1373-1379.
Reis FM, Luisi S, Abrao MS, Rocha AL, Vigano P, Rezende CP, Florio P, Petraglia F: Diagnostic value of serum activin A and follistatin levels in women with peritoneal, ovarian and deep infiltrating endometriosis. Hum Reprod 2012;27:1445-1450.
Mahnke JL, Dawood MY, Huang JC: Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis. Fertil Steril 2000;73:166-170.
Akira S, Taga T, Kishimoto T: Interleukin-6 in biology and medicine. Adv Immunol 1993;54:1-78.
Tsudo T, Harada T, Iwabe T, Tanikawa M, Nagano Y, Ito M, Taniguchi F, Terakawa N: Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues. Fertil Steril 2000;73:205-211.
Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ: Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 1996;271:736-741.
Schroder W, Gaetje R, Baumann R: Interleukin-6 and soluble interleukin-6 receptor in peritoneal fluid and serum of patients with endometriosis. Clin Exp Obstet Gynecol 1996;23:10-14.
Koyama N, Matsuura K, Okamura H: Cytokines in the peritoneal fluid of patients with endometriosis. Int J Gynaecol Obstet 1993;43:45-50.
Vodolazkaia A, El-Aalamat Y, Popovic D, Mihalyi A, Bossuyt X, Kyama CM, Fassbender A, Bokor A, Schols D, Huskens D, Meuleman C, Peeraer K, Tomassetti C, Gevaert O, Waelkens E, Kasran A, De Moor B, D'Hooghe TM: Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod 2012;27:2698-2711.
Mihalyi A, Gevaert O, Kyama CM, Simsa P, Pochet N, De Smet F, De Moor B, Meuleman C, Billen J, Blanckaert N, Vodolazkaia A, Fulop V, D'Hooghe TM: Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers. Hum Reprod 2010;25:654-664.
Hassa H, Tanir HM, Tekin B, Kirilmaz SD, Sahin Mutlu F: Cytokine and immune cell levels in peritoneal fluid and peripheral blood of women with early- and late-staged endometriosis. Arch Gynecol Obstet 2009;279:891-895.
Andreoli CG, Genro VK, Souza CA, Michelon T, Bilibio JP, Scheffel C, Cunha-Filho JS: T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis. Fertil Steril 2011;95:2477-2480.
Nishida M, Nasu K, Narahara H: Role of chemokines in the pathogenesis of endometriosis. Front Biosci (Schol Ed) 2011;3:1196-1204.
Bersinger NA, Dechaud H, McKinnon B, Mueller MD: Analysis of cytokines in the peritoneal fluid of endometriosis patients as a function of the menstrual cycle stage using the Bio-Plex® platform. Arch Physiol Biochem 2012;118:210-218.
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