Abstract
Rheumatoid synovial tissue produces excessive amounts of interleukin-6 (IL-6), which contributes to the immunopathogenesis of rheumatoid arthritis (RA) . In this study we assessed the effect of KE-298, a newly developed anti-rheumatic drug, and its metabolite KE-758 (M-1, deacetylated form) on IL-6 production by synovial fibroblast (SF) . Both KE-298 (25-100μg/ml) and KE-758 (25-100μg/ml) inhibited spontaneous and IL-1 stimulated IL-6 production by SF (spontaneous: KE-298 20%, KE-758 51%, IL-1 stimulated: KE-298 42%, KE-758 47%) . Northern blot analysis showed that KE-758 inhibited IL-1 stimulated IL-6 mRNA expression in SF. To elucidate the mechanism of the inhibitory effects, IL-1β binding assay using SF was performed. 125I-IL-1β binding to SF was inhibited by KE-298 or KE-758 at the concentration of 50-200μg/ml. These data indicate that KE-298 and KE-758 would provide their anti-arthritogenic actions by way of intervening the cytokine network of RA.
