What question did this study set out to answer?

This research aimed to evaluate interleukin levels as noninvasive biomarkers aligned with histological activity in inflammatory bowel disease.

May 2, 2026Open Access

Interleukin signatures as histology-aligned biomarkers in inflammatory bowel disease.

Key Points

This research aimed to evaluate interleukin levels as noninvasive biomarkers aligned with histological activity in inflammatory bowel disease.
Conducted systematic review across MEDLINE, EMBASE, and Web of Science (1995-2025)
Selection of studies reporting interleukin quantification in serum, plasma, stool, or tissue
Assessment of risk of bias and synthesis of findings using narrative methods.
Serum IL-6 and IL-23 had AUC of 0.82-0.86, showing sensitivity / specificity of approximately 75-80% and up to 92% respectively.
Tissue IL-23/IL-17A correlated with neutrophils and detected subclinical inflammation, particularly in ileal Crohn's disease.
IL-10 levels inversely predicted disease activity and longer flare-free survival, aiding remission stability.

Abstract

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, and Web of Science were searched (January 1995–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. Due to assay heterogeneity, narrative synthesis was performed. Results: Sixty-four adult cohorts were included. Serum IL-6 (AUC 0.82–0.85; sensitivity/specificity ≈75–80%) and IL-23 (AUC 0.84–0.86; specificity up to 92%) consistently discriminated histological activity. 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. Interleukin profiling complements CRP and fecal calprotectin, with its immediate role in precision-medicine stratification rather than replacement of current standards. Key Messages:Histological remission is the most reliable endpoint in inflammatory bowel disease but requires invasive biopsies. Interleukin 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. Interleukin signatures therefore complement C-reactive protein and fecal calprotectin, supporting precision-medicine strategies for individualized monitoring and therapy optimization in IBD.

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Martinos et al. (Tue,) studied this question.

synapsesocial.com/papers/69f593f271405d493affed73 https://doi.org/https://doi.org/10.1159/000552149

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