Role of IL-33 and IL-35 in the Pathogenesis of Rheumatoid Arthritis

Cytokine-mediated immunity plays an important role in the pathogenesis of the rheumatoid arthritis. Interleukins IL-33 and IL-35 are closely associated with various rheumatic diseases. The effect of IL-33 on rheumatoid arthritis is believed to be mediated by induction of proinflammatory cytokines (IFN-γ, TNF-α, and IL-17), activation of mast cell degranulation, and mobilization of neutrophils in the joints. However, in addition to the pro-inflammatory, its anti-inflammatory role in rheumatic diseases has also been noticed. The potential mechanism of its anti-inflammatory action can be explained by IL-33-induced mast cell activation that can affect rheumatoid arthritis. IL-35 is a heterodimeric protein and has a significant anti-inflammatory effect. This inhibitory cytokine can express its therapeutic potential through the suppression of osteoclastogenesis and angiogenesis. This review presents current knowledge on the role of these cytokines in the pathogenesis of rheumatoid arthritis.