{"paper_id":"1068fad1-77db-48b7-af97-ef4323dbdfec","body_text":"Abstract\nEndometriosis is a gynecological inflammatory disorder characterized by the presence of endometrial tissue outside of the uterus. It affects 10–15% of reproductive aged women, causing pelvic pain and infertility. Existing treatments for endometriosis, including invasive and non-invasive therapies, are plagued by treatment resistance and adverse effects. Dissecting molecular mechanisms or signaling pathways that are involved in the pathophysiology of endometriosis may reveal new molecular targets. IL-6 is classically considered an inflammatory cytokine that is highly expressed in endometriosis. Here, we studied the effect of an anti-IL-6R antibody that interferes with the IL-6 signaling pathway in endometriosis. Endometriosis was induced in c57BL/6 female mice that were subsequently treated with either a murine-specific anti-IL-6 receptor monoclonal antibody (15A7) or IgG2b as a control. We found that there was no change in endometriosis lesion number or volume. However, we observed that the lesion attachment to underlying peritoneum was significantly increased after treatment with the 15A7 antibody, indicating a possible effect on invasion. As expected, IL-6 mediated pathways of p38 MAPK and STAT3 in JAK/STAT signaling were decreased in the anti-IL-6R treatment group compared to isotype control group. There were no differences in N-Cadherin and ICAM between groups. IL-6 had a paradoxical role in endometriosis – preventing or limiting invasion and adhesion.\nSimilar content being viewed by others\nData Availability\nAvailable with Ramanaiah Mamillapalli and Hugh Taylor.\nCode Availability\nNot applicable.\nReferences\nTaylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: clinical challenges and novel innovations. Lancet. 2021;27(10276):839–52. https://doi.org/10.1016/s0140-6736(21)00389-5.\nAgarwal SK, Chapron C, Giudice LC, et al. 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Cell Commun Adhes. 2003;10(3):141–54.\nAcknowledgements\nThis work was supported by NIH U54 HD052668 and Endometriosis Foundation of America AWD0003567.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nEthics declarations\nEthics Approval\nEthics approved by Yale University.\nConsent\nAll authors gave consent to publish the data.\nConflict of interest\nAuthors declared that there are no conflicts of interest.\nAdditional information\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nHan, E., Mamillapalli, R., Cevik, E.C. et al. IL-6 Inhibits Invasion in a Murine Model of Endometriosis. Reprod. Sci. 32, 3557–3566 (2025). https://doi.org/10.1007/s43032-025-01984-7\nReceived:\nAccepted:\nPublished:\nVersion of record:\nIssue date:\nDOI: https://doi.org/10.1007/s43032-025-01984-7","source_license":"public-domain-us","license_restricted":false}