Systemic anti-tumor necrosis factor alpha therapy in rheumatoid arthritis down-regulates synovial tumor necrosis factor alpha synthesis.

摘要: OBJECTIVE: To investigate the hypothesis that tumor necrosis factor alpha (TNFalpha) blockade in rheumatoid arthritis (RA) diminishes synovial synthesis of TNFalpha, interleukin-1alpha (IL-1alpha), and IL-1beta. METHODS: Patients with active RA received a single 10 mg/kg infusion infliximab. Multiple biopsy specimens were obtained from knee day before 14 days later. A modified immunohistochemical method detecting cytokine-producing rather than cytokine-binding cells was applied to determine IL-1alpha, IL-1beta fixed, cryopreserved sections. Computerized image analysis using two different methodologies performed by independent observers blinded identity samples. RESULTS: All 8 patients met American College Rheumatology 20% improvement response criteria (ACR 20) at 2 weeks, half these ACR 50. With few exceptions, there concordance between both regarding direction change immunopositive area fraction for all cytokines analyzed. TNFalpha significantly reduced after treatment (P = 0.05 Karolinska Institute, Stockholm, Sweden; P 0.008 Kennedy London, UK). meeting 50 those highest baseline levels synthesis. There significant correlation expression therapy. Both IL-1alpha 3 patients; alone patients. In 1 patient, neither nor reduced. CONCLUSION: Analysis tissue means immunomorphology clinical trial setting may allow drawing biologically meaningful conclusions. Synovial weeks infliximab treatment. Reductions demonstrated subgroup High production prior predict responsiveness