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-1 beta in vitro was studied. TRK-530 at a concentration of 10(-4) M inhibited LPS-induced IL-1 beta 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-1 beta production may partly participate the anti-rheumatoid action of TRK-530.
Takaoka
Y
Y
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Nagai
H
H
Mori
H
H
Tanahashi
M
M
D000818:Animals; D000917:Antibody Formation; D001168:Arthritis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D003094:Collagen / Q000009:adverse effects; D004164:Diphosphonates / Q000627:therapeutic use*; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA
D004164:Diphosphonates; D007375:Interleukin-1; C109548:TRK 530; D003094:Collagen