Abstract Background Ulcerative colitis (UC) is driven by a dysregulated mucosal immune response. Interleukins (ILs) orchestrate both pro-inflammatory and regulatory pathways, but their systemic profiles before therapeutic intervention remain unclear. Identifying early cytokine signatures may help stratify disease and guide precision immunotherapy. This meta-analysis aimed to characterise the serum interleukin landscape of treatment-naïve adult UC. Methods A systematic review and meta-analysis was conducted in accordance with PRISMA. PubMed, Scopus, Embase and Web of Science were searched from database January 1995 to September 2025 for studies assessing serum interleukins in untreated UC versus healthy controls. Inclusion criteria: adults ≥18 years; confirmed UC; treatment-naïve at sampling; extractable mean, SD and sample size for IL-17A, IL-8, IL-23 or IL-10; and healthy controls. Exclusion criteria: paediatric cohorts, tissue-only cytokine assays, interventional studies, unavailable quantitative data, and studies on IL-6, IL-1β or IL-33 due to predefined heterogeneity. Standardised mean differences (SMDs) with 95 % confidence intervals (CIs) were pooled using random-effects models (DerSimonian–Laird). Between-study heterogeneity (I²) and publication bias (Egger’s test) were assessed. Analyses were conducted in IBM SPSS Statistics v30.0. Results Eighteen studies met eligibility criteria (5 IL-17A, 5 IL-8, 4 IL-23, 4 IL-10). Compared with healthy controls, treatment-naïve UC showed: • IL-23: SMD 4.08 (95% CI 3.30–4.86; p0.0001; I²=46%) • IL-17A: SMD 2.07 (1.48–2.66; p0.0001; I²=60%) • IL-8: SMD 2.03 (1.27–2.79; p0.0001; I²=0%) • IL-10: SMD −2.57 (−3.27—1.88; p0.0001; I²=0%) These findings indicate a reproducible pattern of increased IL-23, IL-17A and IL-8, accompanied by reduced IL-10, in untreated UC across independent cohorts. Conclusion Across available studies, treatment-naïve UC demonstrates consistent serum cytokine changes characterised by higher IL-23, IL-17A and IL-8 and lower IL-10 compared with healthy controls. This pattern may reflect upstream immune pathway activity in early disease and could support further evaluation of serum interleukins as potential non-invasive biomarkers in UC. References: 1. Liu X, Chen H, Shao L, et al. Updated cytokine profiling in ulcerative colitis. Front Immunol. 2023;14:1123456. 2. Lucaciu O, Copotoiu C, Copotoiu R, et al. Serum cytokine profiles in inflammatory bowel disease. J Immunol Res. 2021;2021:1-10. 3. Akpinar H, Yilmaz B, Dogruel N, et al. Serum IL-23 and IL-10 levels differentiate ulcerative colitis from controls. Eur J Gastroenterol Hepatol. 2020;32(8):1032-1040. 4. Zuo L, Li Y, Wang H, et al. Serum inflammatory cytokines in ulcerative colitis. World J Gastroenterol.2015;21(27):8271-8281. Conflict of interest: Dr. Martinos, Nikolaos: No conflict of interest Lazaris, Andreas C.: No conflict of interest Kroupis, Christos: No conflict of interest Kranidiotis, Georgios: No conflict of interest Stefanidis, Gerasimos: No conflict of interest Vasileiadis, Konstantinos: No conflict of interest Karakoidas, Christos Andreas: No conflict of interest Spyridon, Sgouros: No conflict of interest Thomopoulou, Georgia-Eleni: No conflict of interest
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