OBJECTIVES: Recent evidence suggests a role for interleukin (IL)-33 and its receptor ST2 in arthritis. In this study, we quantified IL-33 and soluble (s)ST2 levels in serum and synovial fluid (SF), and assessed synovial IL-33 expression levels and pattern in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or osteoarthritis (OA). METHODS: Serum and SF IL-33 and sST2 levels were assessed by ELISA. IL-33 mRNA was quantified by RT-qPCR. Synovial IL-33 protein expression pattern was examined by immunohistochemistry. RESULTS: Serum and SF IL-33 levels tended to be higher in RA than in OA patients. In contrast to RA, IL-33 was not detectable in PsA serum and SF. Serum sST2 levels were higher in RA than in OA. There was a wide variation of synovial tissue IL-33 mRNA expression within each disease group and IL-33 mRNA levels were not significantly different between the groups. A similar IL-33 protein expression pattern was observed in RA, PsA and OA synovium, with strong nuclear expression of IL-33 in endothelial cells and, in a subset of RA, PsA and OA patients, in cells morphologically consistent with synovial fibroblasts. DISCUSSION/CONCLUSIONS: This study confirms increased circulating IL-33 levels in RA. In addition, we report that IL-33 is undetectable in the serum or SF of PsA patients. Local expression of IL-33 in the synovium was observed at similar variable levels in RA, PsA and OA, suggesting that inflamed joints do not represent the primary source of elevated serum and SF levels of IL-33 in RA.