Stage-dependent shifts in peritoneal cytokine profiles drive monocyte functional reprogramming in endometriosis

Sofia Shifon, Т. В. Тыринова, Tatyana Veretelnikova, Aleksandra Maksimova, И. М. Ращупкин, Н. М. Пасман, Е. Р. Черных
In: Biomarkers · 2026 · pp. 1–21 · doi:10.1080/1354750x.2026.2718915 · W7202361807
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This study found that stage-dependent shifts in peritoneal fluid cytokines reprogram monocytes from a pro-inflammatory to an immunosuppressive phenotype in endometriosis, with Th2 cytokines correlating with disease severity markers.

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Abstract

Introduction. Endometriosis is a chronic inflammatory disease in which monocytes/macrophages play a key pathogenetic role. The peritoneal fluid (PF) cytokine profile can modulate recruited monocyte functions, determining their contribution to disease progression.Aim. To investigate stage-specific changes in the PF cytokine profile and their impact on functional reprogramming of monocytes in endometriosis.Methods. The study included 26 patients with endometriosis (stages I–III) and 6 controls. PF cytokine concentrations were measured by multiplex analysis (Bio-Plex). The effect of PF on MerTK, CCR2, PD-1, and PD-L1 expression by healthy donor monocytes was assessed by flow cytometry.Results. PF composition changed dynamically with disease stage: at stage I, RANTES and IL-6 increased; at stage II, IL-12 decreased and IL-1ra increased; at stage III, IFN-γ and IL-12 decreased. Stage I PF inhibited MerTK expression on monocytes, whereas stages II–III PF upregulated MerTK, PD-L1, PD-1, and CCR2. Pro-inflammatory cytokines negatively correlated with MerTK and PD-1 changes, while Th2 cytokines positively correlated with MerTK expression. Th2 cytokine levels were directly associated with serum CA-125 concentration.Conclusion. Stage-specific shifts in the PF cytokine profile initiate switching of monocytes from a pro-inflammatory to an immunosuppressive phenotype.

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