Imbalance between Endogenous Antioxidants and Cellular Signaling Pathways in Immune-Mediated Diseases

Abstract

There was growing evidence that many immune-mediated diseases were associated with chronic disturbances in cellular redox balance, which led to persistent inflammation. This paper reviewed the mechanisms linking reactive oxygen and nitrogen species (ROS/RNS), antioxidant defense systems, and redox-sensitive signaling pathways in these conditions. Meta-analyses showed consistent elevations in oxidative and nitrosative stress markers such as lipid peroxidation and protein oxidation alongside reduced antioxidant levels in affected patients. This depletion prolonged exposure to reactive species, increased biomolecular damage, and reinforced inflammatory cycles.Redox imbalance was also associated with sustained activation of pro-inflammatory pathways such as NF-κB, along with inadequate compensatory antioxidant responses through Nrf2-related pathways. This signaling mismatch contributed to continuous cytokine production, immune hyperactivation, and failure to resolve inflammation. The findings suggested that future therapeutic strategies should focus on restoring endogenous antioxidant systems and modulating redox-sensitive inflammatory signaling rather than relying solely on general antioxidant supplementation. Standardized biomarkers were also considered necessary to support the development of targeted redox-based therapies.