Session Title: Rheumatoid Arthritis - Animal Models
Session Type: Abstract Submissions (ACR)
Background/Purpose: : IL-1ß signalling has critical role on pathogenesis of various inflammatory arthritis including rheumatoid arthritis (RA). We aimed to investigate the therapeutic effects of human IL-1 receptor antagonist with Fc fragment (hIL-1Ra-Fc) on autoimmune arthritis and find out the possible mechanisms by which hIL-1RA-Fc has anti-arthritic effects in a murine model of RA and arthritis patient.
Methods: Collagen-induced arthritis (CIA) murine model was induced in DBA/1J mice. The levels of various cytokines were determined by using enzyme-linked immunosorbent assay. The joints of mouse were assessed for clinical arthritis score and histologic features. Th17 cells and Treg cells were stained by using antibodies specific for CD4, IL-17, CD25, and FoxP3. Osteoclastogenesis was determined by TRAP stain and real-time PCR.
Results: hIL-1RA-Fc reduced the clinical arthritis, histological inflammation and cartilage score in CIA model. The expression of proinflammatory cytokines, VEGF, and RANK were reduced in affected joint of hIL-1Ra-Fc treated mice. hIL-1Ra-Fc treated mice showed decreased number of Th17 cells with increased Treg cells in spleens. hIL-1Ra-Fc reduced Th17 cell differentiation by inactivation of STAT-3 signalling, reciprocally induced Treg cell differentiation through STAT-5 signalling. In addition, Suppression of gene expression of IL-17, TNF-α, RANKL and VEGF were decreased, while increased Foxp3 gene expression in PBMC of RA patients after administration of hIL-1Ra-Fc.
Conclusion: The anti-arthritis effects of hIL-1RA-Fc are associated with regulating balance between Th17 cells and Treg cells and with suppressing osteoclastogenesis and angiogenesis in affected joints.
H. K. Min,
S. H. Park,
M. L. Cho,
J. H. Ju,
S. K. Kwok,
S. Y. Lee,
S. M. Jung,
K. S. Park,
« Back to 2014 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/il-1-receptor-antagonis-il-1ra-fc-ameliorate-autoimmune-arthritis-by-regulation-of-the-th17-cellstreg-balance-and-arthrogenic-cytokine-activation/