title: Effects and mechanisms of potent caspase-1 inhibitor VX765 treatment on collagen-induced arthritis in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. scitougao@sina.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000201:enzymology / Q000517:prevention & control*; D001175:Arthrography / Q000379:methods; D015415:Biomarkers / Q000097:blood; D020170:Caspase 1 / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology*; D003094:Collagen; D004151:Dipeptides / Q000494:pharmacology*; D018450:Disease Progression; D018836:Inflammation Mediators / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D000067596:Interleukin-33 / Q000097:blood; D007596:Joints / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008811:Mice, Inbred DBA; D012720:Severity of Illness Index; D013997:Time Factors; D055114:X-Ray Microtomography; D062366:para-Aminobenzoates / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D061945:Caspase Inhibitors; D004151:Dipeptides; C587672:IL1B protein, mouse; C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D020382:Interleukin-18; D053583:Interleukin-1beta; D000067596:Interleukin-33; D062366:para-Aminobenzoates; C520022:belnacasan; D003094:Collagen; D020170:Caspase 1