The Effect of TRK-530 on Experimental Arthritis in Mice

TRK-530 is a newly synthesized diphosphonate derivative. We investigated the effect of TRK-530 on type II collagen-induced arthritis (CIA) in mice in comparison to that of prednisolone and indomethacin. TRK-530 at a dose of 25 mg/kg showed a tendency to inhibit CIA. TRK-530 at a dose of 50 mg/kg inhibited the development of the CIA in terms of the progression of footpad swelling, bone damage and histopathological changes. TRK-530 at a dose of 50 mg/kg also significantly inhibited the delayed type hypersensitivity (DTH) response to type II collagen, but not the production of anti-type II collagen IgG antibody in arthritic mice.To investigate the inhibitory mechanism of TRK-530, the type of effect of TRK-530 on the production of IL-1β in vitro was studied. TRK-530 at a concentration of 10-4M inhibited LPS-induced IL-1β production from J774.1 cells.In conclusion, TRK-530 inhibited CIA in mice. The inhibition of the DTH reaction to type II collagen and the inhibition of IL-1β production may partly participate the anti-rheumatoid action of TRK-530.