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

Ak. Ulfgren et al., Systemic anti-tumor necrosis factor alpha therapy in rheumatoid arthritis down-regulates synovial tumor necrosis factor alpha synthesis, ARTH RHEUM, 43(11), 2000, pp. 2391-2396
Citations number
Categorie Soggetti
Rheumatology,"da verificare
Journal title
ISSN journal
0004-3591 → ACNP
Year of publication
2391 - 2396
SICI code
Objective. To investigate the hypothesis that tumor necrosis factor alpha ( TNF alpha) blockade in rheumatoid arthritis (RA) diminishes synovial synthe sis of TNF alpha, interleukin-1 alpha (IL-1 alpha), and IL-1 beta, Methods. Patients with active RA received a single 10 mg/kg infusion of inf liximab, Multiple synovial biopsy specimens were obtained from a knee the d ay before infusion and 14 days later. A modified immunohistochemical method detecting cytokine-producing rather than cytokine-binding cells was applie d to determine synthesis of TNF alpha, IL-1 alpha, and IL-1 beta in fixed, cryopreserved sections. Computerized image analysis using two different met hodologies was performed by independent observers blinded to the identity o f samples. Results. All 8 patients met the American College of Rheumatology 20% improv ement response criteria (ACR 20) at 2 weeks, and half of these patients met the ACR 50. With a few exceptions, there was concordance between both imag e analysis methodologies regarding the direction of change in immunopositiv e area fraction for all cytokines analyzed. TNF alpha synthesis was signifi cantly reduced after treatment (P = 0.05 at the Karolinska Institute, Stock holm, Sweden; P = 0.008 at the Kennedy Institute, London, UK). Patients mee ting the ACR 50 were those with the highest baseline levels of TNF alpha sy nthesis. There was a significant correlation between baseline levels of TNF alpha expression and change in TNF alpha levels in response to therapy. Bo th IL-1 alpha and IL-1 beta synthesis were reduced in 3 patients; IL-1 alph a synthesis alone was reduced in 2 patients and IL-1 beta synthesis alone w as reduced in 2 patients. In 1 patient, neither IL-1 alpha nor IL-1 beta sy nthesis was reduced. Conclusion, Analysis of synovial tissue by means of immunomorphology and im age analysis in a clinical trial setting may allow the drawing of biologica lly meaningful conclusions. Synovial TNF alpha synthesis was reduced 2 week s after infliximab treatment. Reductions in IL-1 alpha and IL-1 beta synthe sis were demonstrated in a subgroup of patients. High levels of synovial TN F alpha production prior to treatment may predict responsiveness to therapy .