Interleukin Signatures as Prognostic Biomarkers in Ulcerative Colitis: From Immune Pathways to Clinical Prediction

Ulcerative colitis (UC) is a chronic immune-mediated inflammatory disease characterized by substantial heterogeneity in histologic activity, which is frequently uncoupled from clinical symptoms and endoscopic findings. Persistent microscopic inflammation is increasingly recognized as a critical determinant of relapse, therapeutic failure, and long-term disease outcomes, underscoring the need for molecular frameworks that align directly with tissue-level immune dysregulation. Interleukins (ILs) represent central regulators of mucosal immunity in UC, integrating innate and adaptive immune responses that govern epithelial injury and resolution. In this narrative review, we synthesize mechanistic, translational, genetic, and clinical evidence examining IL networks associated with histologic disease activity and persistence. Particular emphasis is placed on IL-23-driven inflammatory pathways, which consistently align with histologic severity, sustained microscopic inflammation, and resistance to immune resolution. In contrast, preserved IL-10-mediated regulatory signaling characterizes histologic remission and effective mucosal healing, whereas its insufficiency permits ongoing tissue-level inflammation. Downstream effector ILs, including IL-6, IL-1β, IL-8, and IL-17A, are discussed as mediators translating upstream immune imbalance into neutrophil recruitment and epithelial injury. Throughout this review, the term "prognostic" is used to denote alignment with histologic disease behavior rather than validated prediction of clinical outcomes. Collectively, the evidence supports the concept that coordinated IL patterns reflect distinct immunopathologic states underlying microscopic inflammation in UC, providing a biologically coherent framework for interpreting histologic activity and disease persistence beyond symptom-based assessment.