Inflammatory and Antioxidant Pathways Intersecting in Chronic Disease: A Unified Mechanistic Framework

Abstract

Chronic diseases such as type 2 diabetes, cardiovascular disease, autoimmune disorders, neurodegeneration, chronic kidney disease, and non-alcoholic fatty liver disease share common biological drivers that transcend organ-specific pathology. Among the most central of these drivers is the dynamic interplay between inflammatory signaling and antioxidant defense systems. Inflammation and oxidative stress are not independent processes; rather, they form an integrated network of reciprocal activation in which reactive oxygen species amplify inflammatory cascades, while inflammatory mediators further enhance oxidative burden. This bidirectional relationship contributes to cellular dysfunction, tissue remodeling, fibrosis, and metabolic derangements that characterize chronic illness. Key molecular nodes-including nuclear factor kappa B (NF-κB), nuclear factor erythroid 2–related factor 2 (Nrf2), inflammasomes, mitochondrial signaling pathways,and redox-sensitive kinases-serve as regulatory hubs within this network. Dysregulation of these systems results in sustained immune activation and impaired antioxidant responses, fostering disease progression across multiple organs. This review synthesizes current knowledge on inflammatory and antioxidant pathway crosstalk, highlighting shared mechanisms across chronic diseases and discussing therapeutic implications of targeting this integrated network. By framing chronic disease through a unified mechanistic lens, we propose a systems-based approach that may inform biomarker development and multi-target therapeutic strategies. Keywords: Oxidative stress, Chronic inflammation, Nrf2 signaling, NF-κB pathway, Multimorbidity.