IFN-γ and IL-22 in premature ovarian insufficiency correlation with ovarian reserve markers and pathogenic implications: a cross-sectional study

Abstract

Background: This case-control study aimed to investigate serum immunocytokine profiles and their clinical relevance in premature ovarian insufficiency (POI), with a particular focus on the potential of these cytokines as diagnostic biomarkers. Methods: This case-control study investigated serum immunocytokine profiles in premature ovarian insufficiency (POI) using 28 patients and 17 controls from Guangxi Reproductive Hospital (2023–2024). Hormones (FSH, LH, E2, AMH, PRL, T) were measured by electrochemical luminescence and cytokines (IFN-γ, IL-1β, IL-6, IL-9, IL-17 A, IL-22, TGF-β1) by ELISA. Results: POI patients exhibited higher FSH/LH and lower E2/AMH/PRL/T (all P < 0.05) versus controls, with increased menstrual irregularity (28.57% vs. 0%, P = 0.043). Distinct cytokine elevation occurred in IFN-γ and IL-22 (both P < 0.05), while other cytokines showed no differences. Menstrual regularity subgroups displayed comparable cytokine profiles despite divergent FSH/LH (P < 0.05), suggesting independent hypothalamic-pituitary-ovarian and immune dysregulation. IFN-γ/IL-22 positively correlated with FSH (r = 0.431/0.476) and POI status (r = 0.314/0.395), while inversely relating to AMH (r=-0.298/-0.345) and PRL (r=-0.382/-0.323) (all P < 0.05). ROC analysis demonstrated diagnostic potential: IFN-γ (AUC = 0.687, 95%CI:0.522–0.852, P = 0.037) and IL-22 (AUC = 0.735, 95%CI:0.574–0.897, P = 0.009). Conclusion: POI features a unique immunocytokine signature with elevated IFN-γ/IL-22 that correlates with ovarian reserve depletion and shows diagnostic promise. The dissociation between menstrual cyclicity and cytokine patterns implies distinct endocrine-immune pathophysiological mechanisms, positioning these cytokines as potential biomarkers for POI diagnosis and mechanistic research.