This study was performed to evaluate the effects of the TNF-alpha inhibitor etanercept on oxidation stress markers representing DNA damage, lipid peroxidation, and protein glycosylation. Twenty-two rheumatoid arthritis (RA) patients underwent etanercept treatment. The levels of serum total, urinary total, and urinary free pentosidine, which is an advanced glycation end-product (AGE), of urinary N(epsilon)-hexanoyl lysine (N(epsilon)-HEL), and of 8-hydroxy-deoxy guanosine (8-OHdG) were measured at baseline and at 3 and 6 months after the initial treatment with etanercept. Serum total and urinary total pentosidine levels were reduced at 6 months after the initial treatment with etanercept, and urinary free pentosidine levels were reduced at 3 and 6 months. Urinary N(epsilon)-HEL levels were also reduced at 3 and 6 months, and urinary 8-OHdG levels were reduced at 6 months. Serum total and urinary total pentosidine levels in RA patients correlated with the number of swelling joints and tender joints, and urinary total pentosidine levels correlated with the Disease Activity Score using 28 joints (DAS28). This study demonstrated that etanercept acts as a regulator against pentosidine formation, oxidative DNA damage, and lipid peroxidation in RA patients.

No abstract

The purpose of this study was to analyze the effect of the soluble TNF-alpha receptor etanercept on the serum levels of IL-16, IL-17, IL-23, and macrophage inflammatory protein-3alpha (MIP-3alpha) in rheumatoid arthritis (RA) patients. Twenty-two patients with RA were administered etanercept once or twice a week for more than 6 months, and we evaluated clinical and laboratory parameters and serum levels of IL-16, IL-17, IL-23, and MIP-3alpha at the baseline and at 3 and 6 months. Additionally, the production of IL-23 and MIP-3alpha of cultured synovial cells stimulated with TNF-alpha from RA patients was determined by ELISA. We also used ELISA kits to determine synovial fluid (SF) levels of IL-17, IL-23, and MIP-3alpha in patients with RA, osteoarthritis (OA), pseudogouty arthritis (PGA), and gouty arthritis (GA). A significant decrease in serum levels of IL-23 and MIP-3alpha was observed at 3 and 6 months after initial treatment of etanercept. TNF-alpha induced MIP-3alpha but not IL-23 production in cultured synovial cells from RA patients. SF levels of IL-17, IL-23, and MIP-3alpha in RA patients showed significantly higher levels than those of OA, PGA, and GA patients. This study demonstrated that the reduction of IL-23 and MIP-3alpha production in RA patients was a newly determined function of etanercept.

No abstract

In this study, we investigated the effect of the antitumor necrosis factor alpha (anti-TNF-alpha) antibody, infliximab, combined with methotrexate (MTX) and MTX alone on the serum levels of interleukin (IL)-23 and IL-17 in rheumatoid arthritis (RA) patients. Infliximab combined with MTX was administered to 26 patients with RA (infliximab group), and MTX alone was given to 20 patients with RA (MTX group). We evaluated clinical and laboratory parameters, including the Disease Activity Scores of 28 joints (DAS28) and serum levels of IL-23 and IL-17 at baseline and at 14 and 30 weeks after the initial treatment with these drugs. Single regression analysis was performed between the levels of serum IL-23 and other clinical and laboratory parameters at baseline before the initial treatment with infliximab or MTX. A significant reduction of DAS28 scores was observed in both the infliximab and the MTX group at 14 and 30 weeks after the initial treatment. A significant decrease in serum levels of IL-23 was observed in the infliximab group but not in the MTX group at 14 and 30 weeks after the initial treatment. Serum IL-17 levels did not show a significant change during the follow-up period. At baseline, before the initial treatment with infliximab or MTX, serum IL-23 levels showed a significant correlation with DAS28 and the number of swollen joints. This study indicated that the reduction of serum IL-23 levels in RA patients was a novel action of infliximab.