IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy. Issue 9 (14th May 2010)

• Record Type: Journal Article
• Authors: Verri, Waldiceu A; Souto, Fabrício O; Vieira, Silvio M; Almeida, Sergio C L; Fukada, Sandra Y; Xu, Damo; Alves-Filho, Jose C; Cunha, Thiago M; Guerrero, Ana T G; Mattos-Guimaraes, Rafaela B; Oliveira, Fabíola R; Teixeira, Mauro M; Silva, João S; McInnes, Iain B; Ferreira, Sergio H; Louzada-Junior, Paulo; Liew, Foo Y; Cunha, Fernando Q
• Is Part Of: Annals of the rheumatic diseases. Volume 69:Issue 9(2010)
• Page Start: 1697
• Page End: 1703
• Publication Date: 2010-05-14
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2009.122655
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: Interleukin 33 (IL-33) is a new member of the IL-1 family of cytokines which signals via its receptor, ST2 (IL-33R), and has an important role in Th2 and mast cell responses. This study shows that IL-33 orchestrates neutrophil migration in arthritis. Methods and results: Methylated bovine serum albumin (mBSA) challenge in the knee joint of mBSA-immunised mice induced local neutrophil migration accompanied by increased IL-33R and IL-33 mRNA expression. Cell migration was inhibited by systemic and local treatments with soluble (s)IL-33R, an IL-33 decoy receptor, and was not evident in IL-33R-deficient mice. IL-33 injection also induced IL-33R-dependent neutrophil migration. Antigen- and IL-33-induced neutrophil migration in the joint was dependent on CXCL1, CCL3, tumour necrosis factor α (TNFα) and IL-1β synthesis. Synovial tissue, macrophages and activated neutrophils expressed IL-33R. IL-33 induces neutrophil migration by activating macrophages to produce chemokines and cytokines and by directly acting on neutrophils. Importantly, neutrophils from patients with rheumatoid arthritis successfully treated with anti-TNFα antibody (infliximab) expressed significantly lower levels of IL-33R than patients treated with methotrexate alone. Only neutrophils from patients treated with methotrexate alone or from normal donors stimulated with TNFα responded to IL-33 in chemotaxis. Conclusions: These results suggest that suppression of IL-33R expression in neutrophils, preventing IL-33-induced neutrophil migration, may be an important mechanism of anti-TNFα therapy of inflammation.