Stimulation with recombinant IL-33 increased secretion of CXCL8 and transcription of several other genes.73 Blocking IL1RL1 inhibited induction of some of these by IL-33 suggesting that fibroblasts may be activated by IL-33.74 However, IL-33 also increased transcription of IL-1β in RA synovial fibroblasts.73 As IL-1β can stimulate many of these same transcripts it is currently unclear which effects were the direct result of IL-33 signaling and which were indirectly stimulated by IL-33-driven IL-1β production (Figure 1A). This evidence concerns the gene IL1B and rheumatoid arthritis.