Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis

Introduction As a cytotoxic product of activated monocytes, macrophages, and lymphocytes, tumor necrosis factor alpha (TNF-α)—together with other cytokines and growth factors—is an important component in the immune response of the human organism. In addition, TNF-α plays a central role in neoangiogenesis. Because of its cytotoxicity with regard to several tumor cells and its motility-hindering effect on human sperm, TNF-α is considered to be a significant pelvic mediator of female sterility.

The goal of our study was to determine as to whether or not an increased TNF-α secretion by peritoneal macrophages (PM) can be measured in female patients with endometriosis compared with healthy subjects, and if TNF-α secretion can be correlated with the activity of endometriosis.

During infertility work-up, 100 female patients underwent a diagnostic laparoscopy. In accordance with the rAFS classification as well as from the macroscopic aspect of the degree of activity of the endometriosis, the patients were divided as follows: an endometriosis-free control group with a completely normal pelvic status (n=35) and three groups with increasing stages of endometriosis (n=65). In the control group (Group 1), the TNF-α concentrations (median values with minimum / maximum) were 6.2 pg/ml (1.9/10.2), in Group 2 with rAFS stage I/II less active endometriosis 56.33 pg/ml (39.5/71.2), in Group 3 with rAFS stage I/II but highly active endometriosis 81.41 pg/ml (68.4/98.7), while in Group 4 with rAFS stage III/IV 200,15 pg/ml (182.6/226.8), respectively.

In conclusion, we were able to show that the TNF-α secretion of PM was significantly higher in patients with proven endometriosis compared to the control group. These results were found to be statistically significant and were in accordance with the histological findings. Thus, due to its immunomodulating potential, TNF-α may be a marker of both activity and stage of endometriosis. Similar content being viewed by others

American Fertility Society (1985) Revised American Fertility Society classification of endometriosis: 1985. Fertil Steril 43:351–352 Bartosik D, Viscarello RR, Damjanov I (1984) Endometriosis as an autoimmune disease. Fertil Steril 41 (2 Suppl):15–122S Bartosik D, Jacobs SL, Kelly LJ (1986) Endometrial tissue in peritoneal fluid. Fertil Steril 46:796–800 Becker JL, Widen RH, Mahan CS, Yeko TR, Parsons AK, Spellacy WN (1995) Human peritoneal macrophage and T lymphocyte populations in mild and severe endometriosis. Am J Reprod Immunol 34:179–187 Bedaiwy MA, Falcone T, Sharma RK, Goldberg JM, Attaran M, Nelson DR, Agarwal A (2002) Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial. Hum Reprod 17:426–431 Betjes MG, Tuk CW, Struijk DG, Krediet RT, Arisz L, Hart M, Beelen RH (1993) Interleukin-8 production by human peritoneal mesothelial cells in response to tumor necrosis factor-alpha, interleukin-1, and medium conditioned by macrophages cocultured with Staphylococcus epidermidis. J Infect Dis 168:1202–1210 Beutler B, Cerami A (1989) The biology of cachectin/TNF—a primary mediator of the host response. Annu Rev Immunol 7:625–655 Buyalos RP, Funari VA, Azziz R, Watson JM, Martinez-Maza O (1992) Elevated interleukin-6 levels in peritoneal fluid of patients with pelvic pathology. Fertil Steril 58:302–306 Calhaz-Jorge C, Costa AP, Barata M, Santos MC, Melo A Palma-Carlos ML (2000) Tumour necrosis factor alpha concentrations in the peritoneal fluid of infertile women with minimal or mild endometriosis are lower in patients with red lesions only than in patients without red lesions. Hum Reprod 15:1256–1260 Campbell IG, Thomas EJ (2001) Endometriosis: candidate genes. Hum Reprod Update 7:15–20 Cheong YC, Shelton JB, Laird SM, Richmond M, Kudesia G, Li TC, Ledger WL (2002) IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions. Hum Reprod 17:69–75 D’Hooghe TM, Debrock S (2002) Endometriosis, retrograde menstruation and peritoneal inflammation in women and in baboons. Hum Reprod Update 8:84–88 D’Hooghe TM, Xiao L, Hill JA (2001) Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis. Arch Gynecol Obstet 265:40–44 Donnez J, Casanas-Roux M (1993) Peritoneal endometriosis: new histopathological aspects. In: Brosens I, Donnez J (eds) The current status of endometriosis. Parthenon, London, pp 75–89 Donnez J, Van Langendonckt A, Casanas-Roux F, Van Gossum JP, Pirard C, Jadoul P, Squifflet J, Smets M (2002) Current thinking on the pathogenesis of endometriosis. Gynecol Obstet Invest 54 [Suppl 1]:52–62 Drake TS, Metz SA, Grunert GM, O’Brien WF (1980) Peritoneal fluid volume in endometriosis. Fertil Steril 34:280–281 Eischen A, Duclos B, Schmitt-Goguel M, Rouyer N, Bergerat JP, Hummel M, Oskam R, Oberling F (1994) Human resident peritoneal macrophages: phenotype and biology. Br J Haematol 88:712–722 Eisermann J, Gast MJ, Pineda J, Odem RR, Collins JL (1988) Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery. Fertil Steril 50:573–579 Fakih H, Baggett B, Holtz G, Tsang KY, Lee JC, Williamson HO (1987) Interleukin-1: a possible role in the infertility associated with endometriosis. Fertil Steril 47:213–217 Garcia-Velasco JA, Arici A (1999) Interleukin-8 expression in endometrial stromal cells is regulated by integrin-dependent cell adhesion. Mol Hum Reprod 5:1135–1140 Gazvani R, Templeton A (2002) Peritoneal environment, cytokines and angiogenesis in the pathophysiology of endometriosis. Reproduction 123:217–226 Halme J (1989) Release of tumor necrosis factor-alpha by human peritoneal macrophages in vivo and in vitro. Am J Obstet Gynecol 161:1718–1725 Halme J, Becker S, Haskill S (1987) Altered maturation and function of peritoneal macrophages: possible role in pathogenesis of endometriosis. Am J Obstet Gynecol 156:783–789 Haney A (1987) Endometriosis: pathogenesis and pathophysiology. In: Wilson EA (ed) Endometriosis. Liss, New York, pp 23–51 Haney AF (1993) Endometriosis, macrophages, and adhesions. Prog Clin Biol Res 381:19–44 Haney AF, Muscato JJ, Weinberg JB (1981) Peritoneal fluid cell populations in infertility patients. Fertil Steril 35:696–698 Haney AF, Jenkins S, Weinberg JB (1991) The stimulus responsible for the peritoneal fluid inflammation observed in infertile women with endometriosis. Fertil Steril 56:408–413 Harada T, Enatsu A, Mitsunari M, Nagano Y, Ito M, Tsudo T, Taniguchi F, Iwabe T, Tanikawa M, Terakawa N (1999) Role of cytokines in progression of endometriosis. Gynecol Obstet Invest 47 [Suppl 1]:34–39; discussion 9–40 Iborra A, Palacio JR, Ulcova-Gallova Z, Martinez P (2000) Autoimmune response in women with endometriosis. Am J Reprod Immunol 44:236–241 Kayisli UA, Mahutte NG, Arici A (2002) Uterine chemokines in reproductive physiology and pathology. Am J Reprod Immunol 47:213–221 Keenan JA, Chen TT, Chadwell NL, Torry DS, Caudle MR (1995) IL-1 beta, TNF-alpha, and IL-2 in peritoneal fluid and macrophage-conditioned media of women with endometriosis. Am J Reprod Immunol 34:381–385 Kennedy S, Mardon H, Barlow D (1995) Familial endometriosis. J Assist Reprod Genet 12:32–34 Khorram O, Taylor RN, Ryan IP, Schall TJ, Landers DV, (1993) Peritoneals fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis. Am J Obstet Gynecol 169:1545–1549 Koga K, Osuga Y, Tsutsumi O, Okagaki R, Momoeda M, Yano T, Fujiwara T, Takai Y, Kugu K, Morita Y, Taketani Y (2000) Increased concentrations of soluble tumour necrosis factor receptor (sTNFR) I and II in peritoneal fluid from women with endometriosis. Mol Hum Reprod 6:929–933 Koninckx PR, Kennedy SH, Barlow DH (1998) Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update 4:741–751 Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H (1996) Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility. Hum Reprod. 11, 1542–1551 Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4:752–762 Maas JW, Calhaz-Jorge C, ter Riet G, Dunselman GA, de Goeij AF, Struijker-Boudier HA (2001) Tumor necrosis factor-alpha but not interleukin-1 beta or interleukin-8 concentrations correlate with angiogenic activity of peritoneal fluid from patients with minimal to mild endometriosis. Fertil Steril 75:180–185 Mathur SP (2000) Autoimmunity in endometriosis: relevance to infertility. Am J Reprod Immunol 44:89–95 McLaren J, Prentice A, Charnock-Jones DS, Millican SA, Muller KH, Sharkey AM, Smith SK (1996) Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest 98:482–489 Pessina GP, Paulesu L, Corradeschi F, Luzzi E, Tanzini M, Di Stefano A, Matteuscci G, Bocci V (1993) Production of tumor necrosis factor alpha by rat alveolar macrophages collected after acute cigarette smoking. Arch Immunol Ther Exp (Warsz) 41:343–348 Pizzo A, Salmeri FM, Ardita FV, Sofo V, Tripepi M, Marsico S (2002) Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis. Gynecol Obstet Invest 54:82–87 Rana N, Braun DP, House R, Gebel H, Rotman C, Dmowski WP (1996) Basal and stimulated secretion of cytokines by peritoneal macrophages in women with endometriosis. Fertil Steril 65:925–930 Ryan IP, Tseng JF, Schriock ED, Khorram O, Landers DV, Taylor RN (1995) Interleukin-8 concentrations are elevated in peritoneal fluid of women with endometriosis. Fertil Steril 63:929–932 Sampson J (1921) Perforating hemorrhagic (chocolate) cysts of the ovary, their importance and especially their relation to pelvic adenomas of endometrial type. Arch Surg 3:245–249 Tabibzadeh SS, Santhanam U, Sehgal PB, May LT (1989) Cytokine-induced production of IFN-beta 2/IL-6 by freshly explanted human endometrial stromal cells. Modulation by estradiol-17 beta. J Immunol 142:3134–3139 Wilson TJ, Hertzog PJ, Angus D, Munnery L, Wood EC, Kola I (1994) Decreased natural killer cell activity in endometriosis patients: relationship to disease pathogenesis. Fertil Steril 62:1086–1088 Witz CA (2002) Pathogenesis of endometriosis. Gynecol Obstet Invest 53 [Suppl 1]:52–62 Author information Authors and Affiliations Corresponding author Additional information The first two authors have contributed equally to this publication Rights and permissions About this article Cite this article Richter, O.N., Dorn, C., Rösing, B. et al. Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis. Arch Gynecol Obstet 271, 143–147 (2005). https://doi.org/10.1007/s00404-003-0591-9 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-003-0591-9