Dysregulated T helper cytokines in serum and peritoneal fluid of women with endometriosis-related infertility

Ahsan F, Fadhil Ahsan, Nanda Yuli Rahmawati, Rahmawati NY, Rahmawati N, Ardianta Widyanugraha M, M. Y. Ardianta Widyanugraha, Ardianta Widyanugraha MY, Tunjungseto A, Arif Tunjungseto, Dwiningsih S, Sri Ratna Dwiningsih, Dwiningsih SR, Ashon Sa’adi, Sa'adi A, Ashon Sa'adi, Santoso B, Budi Santoso
Asian biomedicine : research, reviews and news · 2026 · vol. 20(4) , pp. 248–259 · doi:10.2478/abm-2026-0028 · PMID:42960172 · PMC13718365 · W7224341038
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Abstract

BACKGROUND: Endometriosis is a chronic inflammatory condition and is one of the leading causes of infertility. The role of T helper (Th) cytokines in infertility remains largely unexamined, despite their recognized importance in endometriosis. OBJECTIVES: To investigate the serum and peritoneal fluid levels of IL-4, IL-5, IL-10, IL-17A, IL-17F, and IFN-γ in women with endometriosis and to explore their correlations with disease severity. METHODS: Eighty-seven infertile women undergoing diagnostic laparoscopy were included, comprising 44 endometriosis patients and 43 controls with benign gynecologic disorders. Serum and peritoneal cytokines were measured using Enzyme-linked immunosorbent assay. Statistical analyses assessed differences and correlations with clinical parameters. RESULTS: Both serum and peritoneal fluid levels of IL-4 and IL-5 were markedly higher in endometriosis patients compared to controls (P < 0.001). Although serum IL-10 levels did not show significant differences, there was an increase in peritoneal fluid (P < 0.001). Among those with endometriosis, serum levels of IL-4, IL-10, IL-17A, and IL-17F exhibited a positive correlation with the revised American Society for Reproductive Medicine score, while IL-17F indicated an inverse correlation with the Endometriosis Fertility Index (EFI) scores (r = -0.422, P = 0.004). Receiver operating characteristic curve analysis demonstrated that IL-4 and IL-5 effectively distinguished endometriosis cases from controls, with IL-17F also providing significant predictive value for EFI scores (P = 0.015). CONCLUSIONS: Elevated IL-4 and IL-5 levels in endometriosis suggest a Th2-skewed immune response. Meanwhile, the correlation of IL-17A with disease severity and the inverse relationship of IL-17F with fertility scores highlight the complex role of the Th17 response. These findings enhance understanding of cytokine dysregulation in endometriosis and may guide future therapeutic strategies.

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