Yongfeng Zhang1, Yi Zheng2. 1. Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. 2. Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. scitougao@sina.com.
Abstract
OBJECTIVES: VX765, a potent and selective caspase-1 inhibitor, inhibits the release of IL-1, IL-18 and IL-33. In this study we investigated the effect of VX765 treatment on collagen-induced arthritis (CIA). METHODS: Twenty-four mice were randomly divided into three groups of 8: Normal (wild-type), CIA and VX765 (CIA with VX765 treatment) groups. Mice in the VX765 group received intraperitoneal injection of VX765 (100 mg/kg, twice daily) starting at the day of the booster immunisation (week 3) for a duration of 4 weeks. At the end of experiments (week 7), joints clinical scores, radiographic scores and histologic scores were evaluated. Serum IL-1β, IL-18 and IL-33 levels were assessed by ELISA. RESULTS: VX765 prophylactic treatment significantly reduced joints clinical scores, suppressed bone marrow oedema and synovitis at the early stage of CIA, prevented bone erosion in progressive CIA, and decreased histologic scores and serum cytokine levels. CONCLUSIONS: VX765 prophylactic treatment ameliorated the severity and progression of CIA. These findings suggest that caspase-1 is a potential therapeutic target for RA treatment.
OBJECTIVES: VX765, a potent and selective caspase-1 inhibitor, inhibits the release of IL-1, IL-18 and IL-33. In this study we investigated the effect of VX765 treatment on collagen-induced arthritis (CIA). METHODS: Twenty-four mice were randomly divided into three groups of 8: Normal (wild-type), CIA and VX765 (CIA with VX765 treatment) groups. Mice in the VX765 group received intraperitoneal injection of VX765 (100 mg/kg, twice daily) starting at the day of the booster immunisation (week 3) for a duration of 4 weeks. At the end of experiments (week 7), joints clinical scores, radiographic scores and histologic scores were evaluated. Serum IL-1β, IL-18 and IL-33 levels were assessed by ELISA. RESULTS: VX765 prophylactic treatment significantly reduced joints clinical scores, suppressed bone marrow oedema and synovitis at the early stage of CIA, prevented bone erosion in progressive CIA, and decreased histologic scores and serum cytokine levels. CONCLUSIONS: VX765 prophylactic treatment ameliorated the severity and progression of CIA. These findings suggest that caspase-1 is a potential therapeutic target for RA treatment.