Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis
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ORIGINAL ARTICLE
Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis Ahmed A. El-Zayadi 1 & Sara A. Mohamed 1 & Mohammad Arafa 2 & Shereen M. Mohammed 1 & Abdelhady Zayed 1 & Mohamed S. Abdelhafez 1 & Ahmed M. Badawy 1 Received: 9 March 2020 / Accepted: 11 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1β, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immunehistochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis. Keywords Endometriosis . Rat model . Anti-IL-6
Introduction Endometriosis is an estrogen-dependent disease characterized by the existence of endometrial-like tissue (glands and stroma) outside the normal uterine cavity and affects about 10% of women. Because of extravasation of blood from the endometriotic lesions and subsequently peritoneal scarring, the classical clinical picture of endometriosis is principally pain such as chronic pelvic pain, dysmenorrhea, or dyspareunia and infertility which both have deleterious effect on the quality of life of the female [1].
* Ahmed M. Badawy [email protected] 1
Department of Obstetrics and Gynecology, Mansoura University Hospitals, El Gomhouria St., Mansoura City, Dakahlia 35111, Egypt
2
Department of Pathology, Mansoura University, Mansoura, Egypt
Several theories have explained the occurrence of endometriosis, such as coelomic metaplasia theory, Mullerian remnants theory, lymphatic and vascular migration, genetic theory, and immunological causes; however, Sampson’s retrograde implantation th
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