International Travel Medicine Center of Iran International Journal of Travel Medicine and Global Health 2322-1100 14 3 2026 09 01 Glutathione-CRP Inflammatory Index: A Novel Biomarker Differentiating Acute Versus Chronic Inflammation Depth and Clinical Implications via Redox-Immune Pathway Integration 161 169 247029 10.30491/ijtmgh.2025.546618.1506 EN Maher Akl Faculty of Medicine, National Research Lobachevsky State University of Nizhny Novgorod, 603022 Nizhny Novgorod, Russia 0000-0001-5480-1688 Amr Ahmed The public health department, Riyadh First Health Cluster, Ministry of Health, Saudi Arabia. 0000-0003-3477-236X Journal Article 2025 09 12 Background: Chronic inflammation drives pathologies such as prediabetes, type 2 diabetes, colorectal cancer (CRC), severe community-acquired pneumonia (CAP), and liver cirrhosis, yet biomarkers like high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6) may lack specificity for oxidative-inflammatory depth. We hypothesize that the Glutathione-CRP Inflammatory (GCI) Index, combining hsCRP with the reduced to oxidized glutathione (GSH/GSSG) ratio, could improve diagnostic and prognostic precision. Methods: Archival datasets from prediabetes (n=63), type 2 diabetes (n=50), CRC (n=80), CAP (n=267), and liver cirrhosis (n=75) were analyzed. GCI was calculated as (hsCRP/10 mg/L) + (GSSG/(GSH+GSSG)), normalized to 0–100 using clinical ranges (hsCRP 0–10 mg/L, GSSG/(GSH+GSSG) 0–0.1), and evaluated via logistic regression, receiver operating characteristic (ROC) analysis (hypothesizing 0.05–0.15 AUC improvement), LASSO regularization, and Cox proportional hazards models, adjusting for age, BMI, smoking, and medications. Results: GCI scores might differentiate inflammation types, with values potentially reaching 82 in CRC, 85 in CAP non-survivors, and 80 in Child-Pugh B-C cirrhosis, suggesting associations with tumor progression, mortality, or hepatic decompensation.<br>In diabetes, scores could decline from 72 to 58 post-GSH supplementation, indicating therapeutic response. GCI may outperform hsCRP (AUC 0.841 vs. 0.780 in CAP) and volatile IL-6, driven by NF-κB-mediated hsCRP elevation and ROS-induced GSH depletion disrupting Nrf2 antioxidant defenses. Conclusion: The GCI Index could enhance chronic disease assessment, pending prospective validation for integration into clinical panels alongside hsCRP or HbA1c. https://www.ijtmgh.com/article_247029_49cbd6103967e1845ea3876a2875afac.pdf