Objective: Actarit (4-acetylaminophenylacetic acid), developed in Japan, has 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 medication.
Methods: RA primary synovial cells were co-cultured with actarit at 10(-4)-10(-7) M. Their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of actarit on adhesion molecule expression were analyzed by immunofluorescence flow cytometry and cell-cell binding assay.
Results: Spontaneous tumor necrosis factor-alpha and interleukin 1beta secretion 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, actarit down-regulates CD44 and intercellular adhesion molecule 1 expression on fibroblast-like synovial cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial cells resulted in the inhibition of lymphocyte adhesion to RA synovial cells.
Conclusion: The results suggest that actarit acts on RA synovial cells to reduce cell-cell interactions with autologous synovium infiltrating lymphocytes and to inhibit proinflammatory cytokine and MMP production, leading to amelioration of symptoms of RA.