Effects of caspase-1 inhibitor treatment on collagen-induced arthritis in mice / 中华风湿病学杂志

ABSTRACT

Objective We investigated the effect of VX-765 on collagen induced arthritis (CIA).Methods Twenty-four mice were divided into three groupsthe VX-765 prophylaxis group (VX-765),the CIA model group (CIA) and the wild-type control group (Normal).Each group has 8 mice.Mice with CIA were in-tra-peritoneally injected with VX-765 (100 mg/kg,twice a day),mice with CIA and controls were treated with 0.9％ saline.At the end of the study,clinical scores,radiographic scores and histological scores of joints were calculated.Serum cytokine levels including interleukin (IL)-1β,IL-18,IL-33 were assessed by enzyme linked immunosorbent assay (ELISA).The serum cytokines levels between the CIA group and the VX-765 groups were compared using F test.The clinical scores,radiographic scores and pathological scores between the CIA group and the VX-765 group were compared using the Mann-Whitney test.Results The clinical scores of arthritis and the radiographic scores were significantly lower in the VX-765 group (1,1) than the CIA group (6.5,3.5;Q=4.5,2.75,P＜0.05).Compared with the CIA group,the histological analysis (1,5.5;Q=4.75,P=0.000),serum cytokine levels [IL-1β (2.0±1.0) vs (6.9±2.4) pg/ml,IL-18 (75±42) vs (129±48) pg/ml,IL-33 (145.46 vs 287.22) pg/ml] were significantly lower in the VX-765 group (F=27.98,F=17.27,Q=89.72,P＜0.01).Conclusion These findings suggest that caspase-1 is a potential therapeutic target for rheumatoid arthritis.