IL-6 Inhibits Invasion in a Murine Model of Endometriosis

Endometriosis 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. Similar content being viewed by others Data Availability Available with Ramanaiah Mamillapalli and Hugh Taylor. Code Availability Not applicable.

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This work was supported by NIH U54 HD052668 and Endometriosis Foundation of America AWD0003567. Author information Authors and Affiliations Corresponding author Ethics declarations Ethics Approval Ethics approved by Yale University. Consent All authors gave consent to publish the data. Conflict of interest Authors declared that there are no conflicts of interest. Additional information Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer 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. About this article Cite this article Han, 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 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s43032-025-01984-7