No effects of adalimumab therapy on the activation of NF-kappaB in lymphocytes from patients with severe rheumatoid arthritis.

The aim of this study was to determine the activation level of the pro-inflammatory transcription factor nuclear factor kappaB (NF-kappaB) in lymphocytes of patients with rheumatoid arthritis (RA) before and during an anti-tumor necrosis factor alpha (TNFalpha) therapy (adalimumab). In addition, we analyzed the inflammatory markers, interleukin 6 (IL-6), and C-reactive protein (CRP) and investigated the expression of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibodies in patients' sera. Twenty RA patients and 20 control subjects were investigated. RA patients' characteristics were evaluated by radiography and disease activity score 28 (DAS 28). Twelve weeks of adalimumab therapy was effective in the treatment of RA patients, as shown by a significant improvement of the DAS 28. The inflammatory markers IL-6 and CRP were significantly different in sera of RA patients compared to the control group before the onset of therapy and exhibited a tendency to return to normal levels during the first 12 weeks of therapy. We measured a comparable activation level of NF-kappaB in lymphocytes of control subjects and of RA patients before starting adalimumab therapy. During the following 12 weeks, no significant changes in the activation levels of both NF-kappaB subunits were detected. Serum concentration of RF was significantly lower after 12 weeks, whereas anti-CCP antibody level remained constant.

An evaluation of anti-TNF-alpha-therapy in patients with ankylosing spondylitis: imbalanced activation of NF kappa B subunits in lymphocytes and modulation of serum cortisol concentration.

The aim of this study was to analyse patients with ankylosing spondylitis (AS) during the course of infliximab therapy. The molecular effects were evaluated using lymphocytes and sera that were isolated before therapy began, then again after 2 and 12 weeks from 17 AS patients and compared to those of 24 healthy control individuals. All 17 AS patients responded to treatment with infliximab as assessed using BASDAI. Elevated serum levels of IL-6, CRP and cortisol were reduced to normal levels by the 12 weeks time point. The level of DNA-binding p65 was decreased during the course of infliximab therapy whereas the level of DNA-binding p50 remained elevated until the 12 weeks time point. Taken together, Infliximab is an effective treatment for AS and results in decreased levels of the inflammation markers IL-6 and CRP, and of endogenous cortisol concentration. Unequal alterations in the levels of activated NF-kappaB subunits p50 and p65 might provide insights into the mechanisms of NF-kappaB action and anti-TNF-alpha therapy in AS.