OBJECTIVES: RA is the most common form of inflammatory arthritis. IL-19 acts as a pro-inflammatory cytokine involved in the pathogenesis of RA. We investigated whether anti-IL-19 antibody treatment would modulate the severity of the disease in a CIA rat model. METHODS: We generated a CIA model by immunizing rats with bovine type II collagen. CIA rats were s.c. treated with anti-IL-19 antibody 1BB1. The effects of 1BB1 on CIA rats were determined by hind-paw thickness, severity score, bone destruction, BMD and cytokine production, which were evaluated using radiological scans, micro-CT, real-time quantitative PCR and ELISA. To analyse gene regulation by IL-19, rat synovial fibroblasts (SFs) were isolated and analysed for the expression of TNF-α, IL-1β and RANK ligand (RANKL). RESULTS: In vivo, IL-19 was highly expressed in the synovial tissue and SFs isolated from CIA rats. 1BB1 significantly ameliorated the severity of arthritis by decreasing hind-paw thickness and swelling; prevented bone destruction and bone loss; inhibited the expression of TNF-α, IL-1β, IL-6 and RANKL in synovial tissue; and decreased the production of IL-6 in serum. In vitro, IL-19-induced TNF-α, IL-1β, IL-6 and RANKL expression in CIA SFs. CONCLUSIONS: Specifically blocking IL-19 inhibited pro-inflammatory cytokine production and prevented bone destruction in CIA rats. These findings provide evidence that IL-19 is a novel target, and that anti-IL-19 antibody may be a potential target to ameliorate the severity of RA.
OBJECTIVES:RA is the most common form of inflammatory arthritis. IL-19 acts as a pro-inflammatory cytokine involved in the pathogenesis of RA. We investigated whether anti-IL-19 antibody treatment would modulate the severity of the disease in a CIA rat model. METHODS: We generated a CIA model by immunizing rats with bovine type II collagen. CIA rats were s.c. treated with anti-IL-19 antibody 1BB1. The effects of 1BB1 on CIA rats were determined by hind-paw thickness, severity score, bone destruction, BMD and cytokine production, which were evaluated using radiological scans, micro-CT, real-time quantitative PCR and ELISA. To analyse gene regulation by IL-19, rat synovial fibroblasts (SFs) were isolated and analysed for the expression of TNF-α, IL-1β and RANK ligand (RANKL). RESULTS: In vivo, IL-19 was highly expressed in the synovial tissue and SFs isolated from CIA rats. 1BB1 significantly ameliorated the severity of arthritis by decreasing hind-paw thickness and swelling; prevented bone destruction and bone loss; inhibited the expression of TNF-α, IL-1β, IL-6 and RANKL in synovial tissue; and decreased the production of IL-6 in serum. In vitro, IL-19-induced TNF-α, IL-1β, IL-6 and RANKL expression in CIA SFs. CONCLUSIONS: Specifically blocking IL-19 inhibited pro-inflammatory cytokine production and prevented bone destruction in CIA rats. These findings provide evidence that IL-19 is a novel target, and that anti-IL-19 antibody may be a potential target to ameliorate the severity of RA.
Authors: T W Kragstrup; T Andersen; C Holm; B Schiøttz-Christensen; A G Jurik; M Hvid; B Deleuran Journal: Clin Exp Immunol Date: 2015-05 Impact factor: 4.330
Authors: R Scrivo; P Conigliaro; V Riccieri; M Di Franco; C Alessandri; A Spadaro; R Perricone; G Valesini Journal: Clin Exp Immunol Date: 2015-02 Impact factor: 4.330