Objective. To establish whether the clinical efficacy of pulse methylprednisolone (MP; 1,000 mg intravenously) is related to the modulation of proinflammatory cytokines within the peripheral blood, synovial membrane, or synovial fluid compartments.Methods. Eighteen patients with active rheumatoid arthritis (RA) were studied. Peripheral blood (11 patients) and knee synovial fluid (9 patients, 10 knees) were obtained before and at 4 and 24 hours after MP therapy. Interleukin-lp (IL-lp), IL-8, and tumor necrosis factor a (TNFa) were measured by enzyme-linked immunosorbent assay and biologic assays; prostaglandin E, (PGE,) was measured by competitive radioimmunoassay. In 10 patients, arthroscopically directed synovial biopsies were obtained before and at 24 hours after treatment, at disease relapse (4 patients), and after retreatment (1 patient). Membranes were stained by immunohistochemical techniques with monoclonal antibodies against TNFa, IL-8, IL-lp, and the IL-1 receptor antagonist protein (IL-1Ra).Results. MP therapy was associated with a rapid (within 24 hours) and substantial decrease in the expression of TNFa in the lining and sublining regions of the synovial membrane, as well as substantial decreases

Objective. To investigate the effects of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP) on cell adhesion molecule expression on the synovial vascular endothelium in patients with rheumatoid arthritis (RA).Methods. Sequential arthroscopic biopsy samples were taken before and 24 hours after MP administration (10 patients) and at the time of RA flare (2 patients) and after retreatment with MP (1 patient). Immunoperoxidase staining for E-selectin (CD62E), P-selectin (CD62P), intercellular adhesion molecule 1 (ICAM-1; CD54) and platelet-endothelial cell adhesion molecule (PECAM; CD31) was performed, and the staining was quantified by color video image analysis.Results. MP caused a rapid (within 24 hours) and substantial decrease in the expression of E-selectin on the synovial vascular endothelium, with a smaller reduction in ICAM-1 expression on synovial vascular endothelium and the synovial lining. There were no similar effects on synovial membrane P-selectin or PECAM expression.Conclusion. A potential mechanism by which MP