IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy

Verri, W. A. et al. (2010) IL-33 induces neutrophil migration in rheumatoid arthritis and is a target of anti-TNF therapy. Annals of the Rheumatic Diseases, 69(9), pp. 1697-1703. (doi: 10.1136/ard.2009.122655) (PMID:20472598)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Liew, Prof Foo and McInnes, Professor Iain and Xu, Dr Damo and Alves-Filho, Dr Jose and Fukada, Dr Sandra
Authors: Verri, W. A., Souto, F. O., Vieira, S. M., Almeida, S. C. L., Fukada, S. Y., Xu, D., Alves Filho, J. C., Cunha, T. M., Guerrero, A. T. G., Mattos-Guimaraes, R. B., Oliveira, F. R., Teixeira, M. M., Silva, J. S., McInnes, I. B., Ferreira, S. H., Louzada-Junior, P., Liew, F. Y., and Cunha, F. Q.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Annals of the Rheumatic Diseases
Publisher:B M J Group
ISSN (Online):1468-2060
Published Online:14 May 2010
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine