Effectiveness of different immunomodulator agents in the treatment of experimentally induced endometriosis Deneysel endometriozis tedavisinde farklı immünomodülatör ajanların etkinliği Neşe Gül Hilali 1 , Aykut Barut 3 , Ilker Arıkan 3 , Mehmet Harma 3 , Serdar Gergerlioğlu 2 , Müge Harma 3 1 Department of Obstetrics and Gynecology, Özel Uzmanlar Medical Center, Şanlıurfa, Turkey 2 Department of Physiology, Meram Medical School, Selçuk University, Konya, Turkey 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey Address for Correspondence / Yazışma Adresi: Doç. Dr. Mehmet Harma, Department of Obstetrics and Gynecology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey Phone: +90 372 261 25 60 Gsm: +90 532 466 49 91 e.mail: mehmetharma@superonline.com Objective: : We aimed to investigate the effects of levamisole, inter- feron alpha-2b and leuprolide on peritoneal implants in experimen- tally induced peritoneal endometriosis in rats. Material and Methods: Peritoneal endometriosis was induced in 48 rats by Vernon and Wilson’s method. Four weeks after this proce- dure, peritoneal implants were evaluated histopathologically, and rats were randomized to four groups treated respectively with: a) a single 1 mL intraperitoneal dose of 0.9% saline solution (control group); b) a single 1 mg intramuscular dose of leuprolide acetate; c) interferon alpha-2b, 100.000 U intraperitoneally; d) levamisole 2 mg intraperito- neally for 3 days, then 3 days rest, and continuing in this fashion over 6 weeks. Rats were sacrificed six weeks after the initiation of treat- ment, and endometriotic implants were evaluated macroscopically and histopathologically. Microscopic evaluations were scored as (+), (++), (+++) corresponding respectively to normal, mild or severe atrophy of the glands and stromas. Results were evaluated with chi- square test by SPSS 10.0 package program. A value of p <0.05 was considered significant. Results: Comparing treatment groups with the control group, leupro- lide (p <0.05) and interferon alpha-2b (p <0.05) were effective, but levamisole was ineffective (p >0.05). Conclusions: There is substantial evidence that immunologic fac- tors play a role in the pathogenesis of endometriosis, and it could be expected that immunomodulator agents would be useful in its treat- ment. In this group of agents, interferon alpha-2b was effective, but levamisole was ineffective. Further studies will certainly bring more insight into this disease and will determine the effectiveness of differ- ent immunomodulator agents in its treatment. (J Turkish-German Gynecol Assoc 2009; 10: 84-8) Key words: Experimental endometriosis, treatment, levamisole, in- terferon, leuprolide Received: 02 December, 2008 Accepted: 19 February, 2009 Amaç: Deneysel peritoneal endometriozis oluşturulan ratlarda, leva- mizol, interferon alfa-2b ve löprolidin, peritoneal implantlara etkileri- ni araştırmayı amaçladık. Gereç ve Yöntemler: Vernon ve Wilson yöntemi ile 48 ratta perito- neal endometriozis oluşturuldu. Bu işlemden dört hafta sonra perito- neal implantlar histopatolojik olarak değerlendirildi ve ratlar dört gru- ba ayrıldı: a) birinci kontrol grubundakilere tek doz %0.9 salin solüs- yonu, 1 ml, intraperitoneal; b) ikinci gruptakilere tek doz löprolid ase- tat, 1 mg/rat, intramüsküler; c) üçüncü gruptakilere tek doz interferon alfa-2b, 100.000 U, intraperitoneal ve son olarak d) dördüncü grupta- kilere üç gün boyunca levamizol, 2 mg/rat, intraperitoneal, üç gün- lük aralarla altı hafta süreyle verildi. Ratlar altı haftalık ilaç uygulama- ları sonunda sakrifiye edildiler. Endometriotik implantlar makroskopik ve histopatolojik olarak değerlendirildi. Mikroskopik değerlendirmeler, implantların bez ve stromalarının atrofilerine göre normal, hafif ve şid- detli atrofiye karşılık gelecek şekilde sırasıyla (+), (+ +) ve (+ + +) ola- rak skorlandı. Sonuçlar SPSS 10.0 paket programı kullanılarak, χ 2 testi ile değerlendirildi. p<0.05 anlamlı olarak kabul edildi. Bulgular: İlaç uygulanan gruplar kontrol grubu ile karşılaştırıldığın- da, löprolid (p<0.05) ve interferon alfa-2b (p<0.05) etkili, levamizol ise etkisizdi (p>0.05). Sonuç: Endometriozisin patogenezinde immünolojik faktörlerin rol oynadığına dair güçlü kanıt vardır. Tedavide immünomodülatör ilaç- lardan fayda beklenebilir. Bu grup ilaçlardan interferon alfa-2b etkiliy- ken, levamizol etkisizdir. İleri çalışmalar bu hastalığı anlamaya yaraya- cak ve tedavisinde farklı immünomodülatör ajanların etkinliğini belir- leyecektir. (J Turkish-German Gynecol Assoc 2009; 10: 84-8) Anahtar kelimeler: Deneysel endometriozis, tedavi, levamizol, inter- feron, löprolid Geliş Tarihi: 02 Aralık 2008 Kabul Tarihi: 19 Şubat 2009 Abstract Özet Original Investigation 84 Introduction Endometriosis is defined as the presence of a functional en- dometrial layer, with endometrial glands and stroma, outside the uterine cavity. Although it is common, its etiopathology is not known. Research into its pathogenesis has focused on anatomic, hormonal, immunologic and genetic factors (1-4), while the histogenesis of the disease and the survival mecha- nism of ectopic endometrial tissue has not been clearly ex- plained. Endometrial cells that have entered the peritoneal cavity are destroyed by peritoneal cytolysis and cleaning. It has been demonstrated that cytotoxity against endometrial cells is de- creased in women with pelvic endometriosis. As a result of se-