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

Abstract

We analyzed the effects of the new antirheumatic drug KE-298 on monocyte chemoattractant protein (MCP)-1 and regulated on activation normal T-cell expressed and secreted (RANTES) production in rats with adjuvant-induced arthritis and in interleukin (IL)-1beta-stimulated rheumatoid arthritis (RA) synoviocytes. In rats with adjuvant-induced arthritis, the enhanced production of MCP-1 and RANTES and the development of arthritis were suppressed by oral treatment with 100 mg/kg per day of KE-298 for 18 days. Furthermore, KE-298 (10-100 microg/ml) suppressed MCP-1 and RANTES production by IL-1beta-stimulated RA synoviocytes through inhibition of NF-kappaB and AP-1 activation. 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.