Interleukin Signatures as Histology-Aligned Biomarkers in Inflammatory Bowel Disease.

INTRODUCTION

Histological remission is the most predictive endpoint in inflammatory bowel disease (IBD), yet repeated biopsies are invasive. Interleukins (ILs) are emerging biomarkers that may capture histology-aligned activity. We systematically evaluated IL-6, IL-23, IL-17A, IL-1β, IL-8, and IL-10 as diagnostic and prognostic biomarkers in ulcerative colitis (UC) and Crohn's disease (CD).

METHODS

MEDLINE, EMBASE, Scopus, and Web of Science were searched (January 1989-March 2025). Eligible studies quantified ILs in serum, plasma, stool, or tissue and reported diagnostic/prognostic outcomes against validated histology indices. Risk of bias was assessed with QUADAS-2 (diagnostic) and QUIPS (prognostic). Certainty was graded using GRADE. The feasibility of quantitative synthesis for individual ILs was explored; however, differences in assay platforms, reporting metrics, and biological matrices prevented valid statistical pooling.

RESULTS

Twenty-seven adult cohorts met the inclusion criteria. Serum IL-6 and IL-23 consistently showed the strongest diagnostic performance across studies, with reported AUC values generally ranging between approximately 0.80 and 0.86. Tissue IL-23/IL-17A aligned with neutrophils, crypt injury, and apoptosis, detecting subclinical inflammation and forecasting relapse (notably in ileal CD). IL-1β/IL-8 modestly reflected neutrophil-rich lesions. IL-10 inversely correlated with activity and higher remission levels predicted longer flare-free survival.

CONCLUSION

IL-6 and IL-23 are the strongest serum biomarkers for histology-aligned activity; tissue IL-17A adds lesion-level resolution, while IL-10 provides prognostic value. IL profiling may complement CRP and fecal calprotectin (fCal) in future precision medicine strategies but requires further prospective validation before routine clinical application.

KEY MESSAGES: Histological remission is the most reliable endpoint in IBD but requires invasive biopsies. IL profiling offers a biologically specific, noninvasive alternative that aligns with histological activity. Among candidate cytokines, serum IL-6 and IL-23 consistently show the strongest diagnostic performance, while tissue IL-17A enhances lesion-level resolution and IL-10 provides prognostic value for remission stability. IL signatures therefore complement C-reactive protein and fCal, supporting precision medicine strategies for individualized monitoring and therapy optimization in IBD.