Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade

Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses ∼10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1β. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.

[1]  I. Foeldvari,et al.  The German etanercept registry for treatment of juvenile idiopathic arthritis , 2004, Annals of the rheumatic diseases.

[2]  G. Firestein,et al.  Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist , 2004, The Lancet.

[3]  J. Verbsky,et al.  Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. , 2004, The Journal of rheumatology.

[4]  M. Torrisi,et al.  Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: Implications for inflammatory processes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  M. Genovese,et al.  Combination therapy with etanercept and anakinra in the treatment of patients with rheumatoid arthritis who have been treated unsuccessfully with methotrexate. , 2004, Arthritis and rheumatism.

[6]  A Ravelli,et al.  Toward an understanding of the long-term outcome of juvenile idiopathic arthritis. , 2004, Clinical and experimental rheumatology.

[7]  P. Emery,et al.  Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor alpha blockade. , 2004, Arthritis and rheumatism.

[8]  Marlene Wolf,et al.  Chemokines: multiple levels of leukocyte migration control. , 2004, Trends in immunology.

[9]  P. Hawkins,et al.  Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. , 2004, Arthritis and rheumatism.

[10]  D. Kastner,et al.  Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Martini,et al.  Early predictors of outcome in juvenile idiopathic arthritis. , 2003, Clinical and experimental rheumatology.

[12]  A. Naya,et al.  CCR1 chemokine receptor antagonist. , 2003, Current pharmaceutical design.

[13]  A. Prieur,et al.  Efficacy of etanercept for the treatment of juvenile idiopathic arthritis according to the onset type. , 2003, Arthritis and rheumatism.

[14]  Virginia Pascual,et al.  Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood , 2003, The Journal of experimental medicine.

[15]  D. McCurdy,et al.  Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis. , 2003, The Journal of rheumatology.

[16]  R. Schneider,et al.  Long-term efficacy and safety of etanercept in children with polyarticular-course juvenile rheumatoid arthritis: interim results from an ongoing multicenter, open-label, extended-treatment trial. , 2003, Arthritis and rheumatism.

[17]  E. Remmers,et al.  De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. , 2002, Arthritis and rheumatism.

[18]  C. Dinarello,et al.  The IL-1 family and inflammatory diseases. , 2002, Clinical and experimental rheumatology.

[19]  R. Schneider,et al.  Differences in the profiles of circulating levels of soluble tumor necrosis factor receptors and interleukin 1 receptor antagonist reflect the heterogeneity of the subgroups of juvenile rheumatoid arthritis. , 2002, The Journal of rheumatology.

[20]  Y. Iwakura,et al.  Suppression of autoimmune arthritis in interleukin-1-deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells. , 2002, Arthritis and rheumatism.

[21]  K. Onel,et al.  Thalidomide therapy for recalcitrant systemic onset juvenile rheumatoid arthritis. , 2002, The Journal of pediatrics.

[22]  Virginia Pascual,et al.  Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus , 2001, Science.

[23]  P. Woo,et al.  Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. , 2001, Clinical and experimental rheumatology.

[24]  V. Pascual,et al.  Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. , 2001, Science.

[25]  R. Schneider,et al.  Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study. , 2000, Arthritis and rheumatism.

[26]  T. Lehman.  Clinical trials for the treatment of systemic onset juvenile rheumatoid arthritis-juvenile idiopathic arthritis , 2000, Current rheumatology reports.

[27]  Andre Peeters,et al.  Etanercept in children with polyarticular juvenile rheumatoid arthritis , 2000 .

[28]  A. Reiff,et al.  Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. , 2000, The New England journal of medicine.

[29]  R. Cimaz,et al.  Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. , 2000, The Journal of rheumatology.

[30]  S. Nakae,et al.  Development of Chronic Inflammatory Arthropathy Resembling Rheumatoid Arthritis in Interleukin 1 Receptor Antagonist–Deficient Mice , 2000, The Journal of experimental medicine.

[31]  A. Adebajo,et al.  The use of intravenous pulsed methylprednisolone in the treatment of systemic-onset juvenile chronic arthritis. , 1998, British journal of rheumatology.

[32]  A. Stagg,et al.  Inflammatory cytokines and cytokine antagonists in whole blood cultures of patients with systemic juvenile chronic arthritis. , 1998, British journal of rheumatology.

[33]  Wallace Ca,et al.  Juvenile rheumatoid arthritis: outcome and treatment for the 1990s. , 1991 .

[34]  A. Martini,et al.  Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. , 1991, Arthritis and rheumatism.

[35]  C. Wallace,et al.  Juvenile rheumatoid arthritis: outcome and treatment for the 1990s. , 1991, Rheumatic diseases clinics of North America.

[36]  Audrey M. Nelson,et al.  Textbook of Pediatric Rheumatology , 1990 .

[37]  J. Fries,et al.  A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. , 1986, Arthritis and rheumatism.