Disease modifying activity of HWA 486 in rat adjuvant-induced arthritis

HWA 486 was investigated for its ability to modify the development of adjuvant-induced polyarthritis in Lewis rats. HWA 486 (20 mg/kg/day p.o.), dosed for 8 or 16 days beginning with the day of adjuvant administration, significantly reduced edema, fibrinogen levels, and erythrocyte sedimentation rates (ESR) 42 days later. When HWA 486 (20 mg/kg/day, p.o.) and cyclosporin A (CsA 15 mg/kg/day, p.o.) were tested in the 8-day treatment regimen, the antiarthritic effects of HWA 486 were more sustained. Both compounds reduced the delayed hypersensitivity (DTH) response on day 9 followed by a rebound to an enhanced DTH response on day 21. The PHA-induced mitogenic response of splenocytes from arthritic rats was suppressed on day 9. Treatment with HWA 486 but not CsA restored the splenocyte response to the level of the negative controls.