Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E‐selectin and intercellular adhesion molecule 1 expression

Abstract

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

Tumor necrosis factor α blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue

“…Similarly, an open study of 10 RA patients revealed decreased expression of adhesion molecules and chemokines in the synovium, resulting in decreased cell trafficking to the joints, 24 hours after high-dose intravenous pulse corticosteroid treatment (31,32). Consistent with the findings in the present study is the clinical experience that patients may start to feel better very early after initiation of infliximab treatment (4).…”

Effects of pulse methylprednisolone on inflammatory mediators in peripheral blood, synovial fluid, and synovial membrane in rheumatoid arthritis

“…The in vivo studies reported here demonstrate that a major mechanism through which MP mediates its effects in RA is inhibition of TNFa production in the synovial membrane. These results may explain our previous findings that MP dramatically inhibits neutrophil ingress into inflamed joints, resulting in a rapid decrease in synovial fluid neutrophil numbers (6,10), that the neutrophils remaining in the synovial cavity after MP therapy have phenotypic changes consistent with decreased activation since they express more L-selectin and less CDllb on their surface than pretreatment neutrophils (6), and that cell adhesion molecule expression decreases in the synovial membrane following MP treatment (24). A similar decrease in synovial membrane expression of cell adhesion molecules has been demonstrated in response to treatment of RA patients with antibodies to TNFa (26).…”

“…The immunostained sections were examined using a computer-assisted color video image analysis system (Video Pro 32; Leading Edge P/L, Adelaide, South Australia) (23,24), as previously described. At least 2 biopsy samples from a single time point were analyzed, with a minimum of 5 high power fields per time point.…”

Adhesion molecules at the synovial level in rheumatoid arthritis: Comment on the review article by Mojcik and Shevach

“…I would, however, like to take issue with the authors in relation to their statement that synovial fluid (SF) polymorphonuclear cells have been studied less intensively; they have completely overlooked our own published work in this area (2). Corticoste-roids are arguably the most dramatic and effective antiinflammatory treatment available, and we, along with others, have previously shown the dramatic effects of pulse corticosteroid treatment on rheumatoid arthritis (RA) disease activity (3)(4)(5) as well as on neutrophil trafficking into joints (6 1996;3Y: 1077-81.…”