Abstract
Traxanox was inactive against classic acute and subacute inflammation models such as carrageenin paw edema, UV erythema, 6-hr Evans blue-carrageenin (E-C) pleurisy and cotton pellet granuloma formation, and it failed to inhibit the production of prostaglandin E2 and a slow reacting substance from rat peritoneal leucocytes which phagocytize killed bacteria in vitro. On the other hand, traxanox inhibited the anaphylactoid reaction and decreased the pleural fluid in 24-hr E-C pleurisy. Traxanox (100 mg/kg, p.o.) also showed a tendency to suppress dextran edema and cotton pellet granuloma formation in adjuvant arthritis (AA) in rats. In experimental models of delayed type hypersensitivity (DTH), traxanox (100 mg/kg, p.o.) inhibited the accumulation of the exudate and the leucocyte migration in B. pertussis-induced pleurisy in rats. Traxanox (50 mg/kg) did not show any effect on AA in Lewis rats when administered orally for 21 days after the adjuvant inoculation, but the combined administration of traxanox with hydrocortisone (10 mg/kg, p.o.) or indomethacin (0.25 mg/kg, p.o.) resulted in a synergistic inhibition of AA. When the administration of traxanox was started 21 days before the adjuvant inoculation, it inhibited AA in a dose-dependent manner (50 ?? 100 mg/kg, p.o.). On the other hand, traxanox (100 mg/kg, p.o.) enhanced the concanavalin A-induced DTH-like skin reaction in guinea pigs. These results indicate that the mode of action of traxanox on inflammatory responses resembles that of D-penicillamine or levamisole, so that it may prove to be clinically effective in treating rheumatoid arthritis.
