Figure 1.

Schematic of the role of interleukin-33 (IL-33) in the development of rheumatoid arthritis (RA). IL-33 released by synovial fibroblasts under inflammatory conditions [detected in the synovial fluid (SF) and serum samples of RA patients] binds to ST2 on immune cells such as mast cells and lymphocytes (Th2 and B cells) and activates these cells to release inflammatory molecules and antibodies contributing to the pathology of the disease. Pro-inflammatory cytokines released by immune cells such as IL-1β and TNF-α can activate fibroblast cells creating a positive feedback system and thus releasing more IL-33. Meanwhile, expression of IL-33 is also increased during osteoblast differentiation and IL-33 is able to inhibit bone absorption by blocking osteoclast formation, therefore protecting bone in RA. In this setting, IL-33 might be secreted as a result, rather than as a cause, of bone erosion.