Background Rheumatoid arthritis (RA) is characterized by chronic systemic inflammation that can result in oxidative stress. Oxidative stress can then increase the production of superoxides including nitric oxide that lead to the formation of pro-oxidant peroxynitrite. Due to a difficulty in quantifying peroxynitrite, nitrotyrosine is proposed as a surrogate marker for peroxynitrite production. Raised levels of nitrotyrosine have been reported in RA patients. Monocyte chemoattractant protein-1 (MCP-1, or CCL2) is a chemoattractant for monocytes, which are implicated in the pathogenesis of RA or other diseases. The effect of etanercept therapy on changes in nitrotyrosine and MCP-1 in RA patients in terms of amelioration of inflammation remains obscure.
Objectives To investigate the effects of etanercept on the plasma nitrotyrosine and MCP-1 levels.
Methods 40 RA patients failing to respond to conventional DMARDs underwent etanercept (25 mg biw) therapy. Nitrotyrosine and MCP-1 in plasma were quantified by EIAs before, 3m, & 12m after the therapy. 15 age-matched RA patients who did not receive biologics served as controls.
Results A significant decrease in nitrotyrosine was observed 3m & 12m after therapy (both p <0.001) compared to those found in the controls (p=0.296 at 1 yr). On the other hands, a significant increase in MCP-1 was observed also 3m & 12m after the therapy (p=0.001 at 3m and p<0.001 at 12m) compared to those found in the controls (p=0.317 at 1 yr). No patients experienced major side effects including infections or mortality during the treatments.
Conclusions Nitrotyrosine decreased and MCP-1 increased significantly after etanercept therapy in RA patients, suggesting that oxidative stress in RA patients can be effectively attenuated by anti-TNF agents. These effects can occur as early as 3 months. The relationship between the fluctuation of nitrotyrosine and MCP-1 deserves further investigations.
Arnett FC, et al. Arthritis Rheum 1988; 31: 315-24.
Ceriello A, et al. Diabetologia 2001; 44: 834-8.
Hayakawa E, et al. J Atheroscler Thromb 2012; 19: 13-22.
Misko TP, et al. Osteoarthritis Cartilage 2013; 21: 151-6.
Disclosure of Interest None declared