Role of redox imbalance and cytokines in mediating oxidative damage and disease progression of patients with rheumatoid arthritis |
| |
Authors: | Ayan Pradhan Aniruddha Bagchi Soumita De Sneha Mitra Shibabrata Mukherjee Parasar Ghosh |
| |
Affiliation: | 1. Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, India;2. Department of Rheumatology and Clinical Immunology, Institute of Post Graduate Medical Education and Research, Kolkata, India |
| |
Abstract: | Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder wherein the contributory role of oxidative stress has been established in the synovial fluid. As availability of synovial fluid is limited, this study aimed to evaluate in the peripheral blood of patients with RA, the relationship if any, between the extent of oxidative stress in terms of generation of reactive oxygen species (ROS) in neutrophils, plasma NADPH oxidase and myeloperoxidase activity with markers of oxidative damage, circulating cytokines and disease activity score (DAS28). In patients with RA, neutrophils in peripheral blood demonstrated an enhanced generation of ROS, coupled with depletion of free radical scavenging activity. Furthermore, the NADPH oxidase and myeloperoxidase activity was enhanced as were markers of damage. There was a positive correlation between the DAS 28 and generation of ROS, NADPH oxidase and myeloperoxidase activity as also with oxidative stress mediated protein carbonylation. Patients with RA demonstrated an increase in proinflammatory (IL-17, IL-23, and IFN-γ) and some anti-inflammatory (IL-4, IL-5, and TGF-β) cytokines. Although the levels of IL-17 correlated positively with generation of ROS, myeloperoxidase, markers of protein damage and DAS28, IL-23 correlated positively only with protein damage, and negatively with free radical scavenging activity. Importantly, incubation of neutrophils from healthy donors with plasma or SF from patients with RA translated into an enhanced generation of ROS, along with an elevation of intracellular proinflammatory cytokines. Taken together, in patients with RA, circulating neutrophils mediated a shift in the oxidant/antioxidant balance favouring the former, which translated into protein damage and contributed towards disease progression. |
| |
Keywords: | Antioxidants cytokines NADPH oxidase oxidative damage reactive oxygen species rheumatoid arthritis |
|
|