The new antirheumatic drug KE-298 suppresses monocyte chemoattractant protein (MCP)-1 and RANTES production in rats with adjuvant-induced arthritis and in Il-1 beta-stimulated synoviocytes of patients with rheumatoid arthritis

We analyzed the effects of the new antirheumatic drug KE-298 on monocyte ch emoattractant protein (MCP)-1 and regulated on activation normal T-cell exp ressed and secreted (RANTES) production in rats with adjuvant-induced arthr itis and in interleukin (IL)1 beta -stimulated rheumatoid arthritis (RA) sy noviocytes. In rats with adjuvant-induced arthritis, the enhanced productio n of MCP-1 and RANTES and the development of arthritis were suppressed by o ral treatment with 100 mg/kg per day of KE-298 for 18 days. Furthermore, KE -298 (10-100 mug/ml) suppressed MCP-1 and RANTES production by IL-1 beta -s timulated RA synoviocytes through inhibition of NF-kappaB and AP-1 activati on. These results suggest that the inhibitory effect of KE-298 on MCP-1 and RANTES production might partly explain its efficacy in rats with adjuvant- induced arthritis and in patients with RA.