Decrease in cellularity and expression of adhesion molecules by anti–tumor necrosis factor α monoclonal antibody treatment in patients with rheumatoid arthritis

Abstract

Objective. The effect of chimeric anti-tumor necrosis factor a (TNFa) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti-TNFa therapy leads to down-regulation of adhesion molecules and a decrease in inflammatory cell influx in synovial tissue (ST).Methods. The immunohistologic features of synovial biopsy specimens, both before and 4 weeks after anti-TNFa MAb (cA2) therapy, were studied in 14 patients with rheumatoid arthritis (RA). The patients either received a placebo (n = 2), or were given intravenous doses of cA2 at 10 mg/kg (n = 5) or 20 mglkg (n = 7).Results. A significant (P < 0.03) reduction in the mean scores for T cells and for the adhesion molecules, vascular cell adhesion molecule 1 and E-selectin, was observed after therapy with 10 mg/kg or 20 mglkg of cA2 in RA patients. molecules, and the decrease in cellularity of rheumatoid ST after cA2 administration support the hypothesis that the antiinflammatory effect of anti-TNFa therapy might be partly explained by down-regulation of cytokineinducible vascular adhesion molecules in ST, with a consequent reduction of cell traffic into joints. Conclusion. The reduced expression of adhesion

Alefacept treatment in psoriatic arthritis: Reduction of the effector T cell population in peripheral blood and synovial tissue is associated with improvement of clinical signs of arthritis

“…This is consistent with previous studies showing a strong correlation between macrophages and arthritis activity (35,45,51,52). It appears unlikely that alefacept had a direct effect on ST macrophages in light of its specificity.…”

TNFα blockade in human diseases: Mechanisms and future directions

“…TNFα upregulates adhesion molecules on the endothelium, stimulates fibroblast proliferation, and recruits leukocytes from the circulation into the synovial fluid [23]. TNFα stimulates production of other cytokines and chemokines, reactive oxygen intermediates, nitric oxide and prostaglandins, and increases the rate of tissue remodeling by matrix-degrading proteases [24,25]. TNFα promotes angiogenesis and osteoclast differentiation and activates osteoclasts to resorb bone, leading to joint erosions particularly at the marginal surfaces [26,27].…”

“…TNFα promotes angiogenesis and osteoclast differentiation and activates osteoclasts to resorb bone, leading to joint erosions particularly at the marginal surfaces [26,27]. It also increases the rate of tissue remodeling by matrixdegrading proteases [24,25] and directly mediates pain, fever, and cachexia.…”

“…TNFα might play a role in the development of RA-associated cardiovascular disease by increasing endothelial cell expression of adhesion molecules in the synovial tissue [24,25]. Treatment with anti-TNFα agents results in a dosedependent reduction in the expression of endothelial adhesion molecules in the synovial tissue [25] and decreases in soluble forms of intracellular adhesion molecule-1 (ICAM-1) and E-selection [37].…”

Biologic agents for treating rheumatoid arthritis. Concepts and progress

“…Although retreatment with cA2 has been effective, development of human antibodies to cA2 may limit the duration of retreatment responses (69). The mechanism of action of cA2 is still uncertain, but the antiinflamma- tory effects of anti-TNF MAb treatment may result, in part, from down-regulation of cytokine-induced vascular adhesion molecules and reduction of inflammatory cell movement into the joints (70)(71)(72). A humanized anti-TNF MAb is also being evaluated in patients with RA; results from the first study are encouraging (73).…”