IL-1 Receptor Antagonis (IL-1Ra)-Fc Ameliorate Autoimmune Arthritis By Regulation of the Th17 Cells/Treg Balance and Arthrogenic Cytokine Activation

Hong Ki Min¹, Sung Hwan Park², Mi-La Cho³, Ji Hyeon Ju¹, Seung-Ki Kwok⁴, Seon-Yeong Lee³, Seung Min Jung¹, Kyung-Su Park⁵ and Jennifer Lee¹, ¹Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, School of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea, ³Rheumatism Research Center, Catholic Research Institute of Medical Science, Catholic University of Korea, Seoul, South Korea, ⁴Division of Rheumatology, Department of Internal Medicine, St. Mary’s hospital, The Catholic University of Korea, Seoul, South Korea, ⁵Internal Medicine, St. Vincent Hospital, SuWon Gyeonggi-do, South Korea

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Autoinflammatory Disease, IL-1, T cells, T-Regulatory Cells and osteoclastogenesis

Session Information

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.

Disclosure:

H. K. Min,
None;

S. H. Park,
None;

M. L. Cho,
None;

J. H. Ju,
None;

S. K. Kwok,
None;

S. Y. Lee,
None;

S. M. Jung,
None;

K. S. Park,
None;

J. Lee,
None.

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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/