Blocking Interleukin‐33 Alleviates the Joint Inflammation and Inhibits the Development of Collagen‐Induced Arthritis in Mice
Yan Li, Yeqin Fu, Huan Chen, Xiaojin Liu, Mingcai Li
Abstract
Rheumatoid arthritis (RA) is considered a systemic chronic inflammatory joint disease characterized by chronic synovitis and cartilage and bone destruction. Interleukin‐33 (IL‐33) is a proinflammatory cytokine which is highly expressed in the synovium of RA patients and the joints of mice with collagen‐induced arthritis (CIA) and exacerbates CIA in mice. However, the role of the IL‐33‐neutralizing antibody in the murine model of CIA remains unclear. In the present study, CIA mice were given intraperitoneally with polyclonal rabbit anti‐murine IL‐33 antibody (anti‐IL‐33) or normal rabbit IgG control after the first signs of arthritis. Administration of anti‐IL‐33 after the onset of disease significantly reduced the severity of CIA and joint damage compared with controls treated with normal rabbit IgG. Anti‐IL‐33 treatment also significantly decreased the serum levels of interferon‐ γ (IFN‐ γ ),IL‐6, IL‐12, IL‐33, and tumor necrosis factor‐ α (TNF‐ α ). Moreover, anti‐IL‐33 treatment significantly downregulated the production of IFN‐ γ , IL‐6, IL‐12, IL‐33, and TNF‐ α in ex vivo‐stimulated spleen cells. Together, our results indicate that the IL‐33‐neutralizing antibody may provide a therapeutic strategy for RA by inhibiting the release of proinflammatory cytokines.