SIRL-1 deficiency reveals pro-inflammatory IL-8 axis in inflammatory bowel disease: a novel diagnostic ratio

Background: Inflammatory Bowel Disease (IBD), including Ulcerative Colitis and Crohn's Disease, is characterized by chronic intestinal inflammation, neutrophil infiltration and elevated pro-inflammatory cytokines like Interleukin-8 (IL-8). While pro-inflammatory mechanisms are well-studied, the contribution of intrinsic inhibitory immune checkpoints to IBD pathogenesis is less understood. This study aimed to assess the expression and function of Signal Inhibitory Receptor on Leukocytes-1 (SIRL-1) in IBD and to evaluate the diagnostic utility of the SIRL-1/IL-8 ratio. Methods: (SIRL-1 gene) and IL-8 messenger RNA levels were measured by RT-qPCR. Serum IL-8 concentrations were determined using a flow cytometry microbead array. Statistical analyses included Mann-Whitney U tests, Kruskal-Wallis tests, Spearman correlations, and Receiver Operating Characteristic (ROC) curve analysis. Results: = 0.0118). Crucially, the SIRL-1/IL-8 ratio demonstrated superior diagnostic accuracy for distinguishing IBD from healthy controls (AUC = 0.82), outperforming individual markers, and was notably effective in Crohn's Disease (AUC = 0.86). Conclusions: Deficiency in SIRL-1 appears to be a permissive factor for the pro-inflammatory IL-8 axis in IBD. The SIRL-1/IL-8 ratio represents a promising novel diagnostic biomarker that presents enhanced precision by reflecting the imbalance between immune regulation and inflammation. Notably, this ratio revealed superior diagnostic value in Crohn's Disease despite the lack of significant IL-8 elevation, highlighting its utility in capturing intrinsic immune defects.