Effects of actarit on synovial cell functions in patients with rheumatoid arthritis

Objective. Actarit (4-acetylaminophenylacetic acid), developed in Japan, ha s been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA). We analyzed effects of actarit on synovial cell functions in patients with RA for insight into the clinical application of this medic ation. Methods. RA primary synovial cells were co-cultured with actarit at 10(-4)- 10(-7) M. Their subsequent proliferative responses and proinflammatory cyto kine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of actarit on adhesion molecule expression we re analyzed by immunofluorescence flow cytometry and cell-cell binding assa y. Results, Spontaneous tumor necrosis factor-alpha and interleukin 1 beta sec retion by primary synovial cells of patients with RA was reduced by actarit at therapeutic concentrations (10(-5)-10(-6) M). In contrast, actarit also suppressed MMP-1 production by the primary synovial cells. In addition, ac tarit down-regulates CD44 and intercellular adhesion molecule I expression on fibroblast-like synovial cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial cells resulted in the inhibition of lymph ocyte adhesion to RA synovial cells. Conclusion. The results suggest that actarit acts on RA synovial cells to r educe cell-cell interactions with autologous synovium infiltrating lymphocy tes and to inhibit proinflammatory cytokine and MMP production, leading to amelioration of symptoms of RA.