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IL-1 pathways in inflammation and human diseases

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Published in Nature Reviews Rheumatology. 2010, vol. 6, no. 4, p. 232-241
Abstract Interleukin (IL)-1 was first cloned in the 1980s, and rapidly emerged as a key player in the regulation of inflammatory processes. The term IL-1 refers to two cytokines, IL-1alpha and IL-1beta, which are encoded by two separate genes. The effects of IL-1 are tightly controlled by several naturally occurring inhibitors, such as IL-1 receptor antagonist (IL-1Ra), IL-1 receptor type II (IL-1RII), and other soluble receptors. Numerous IL-1 inhibitors have been developed and tested primarily in rheumatoid arthritis, with only modest effects. By contrast, the use of IL-1 antagonists has been uniformly associated with beneficial effects in patients with hereditary autoinflammatory conditions associated with excessive IL-1 signaling, such as cryopyrinopathies and IL-1Ra deficiency. Successful treatment with IL-1 blockers has also been reported in other hereditary autoinflammatory diseases, as well as in nonhereditary inflammatory diseases, such as Schnizler syndrome, systemic-onset juvenile idiopathic arthritis and adult Still disease. The role of microcrystals in the regulation of IL-1beta processing and release has provided the rationale for the use of IL-1 inhibitors in crystal-induced arthritis. Finally, preliminary results indicating that IL-1 targeting is efficacious in type 2 diabetes and smoldering myeloma have further broadened the spectrum of IL-1-driven diseases.
Keywords AnimalsCohort StudiesDisease Models, AnimalDrug Delivery SystemsFemaleHumansInflammation/blood/physiopathologyInflammation Mediators/bloodInterleukin 1 Receptor Antagonist Protein/therapeutic useInterleukin-1/*antagonists & inhibitors/*metabolismInterleukin-1beta/drug effects/metabolismMaleMicePrognosisReceptors, Interleukin/antagonists & inhibitors/drug effectsRheumatic Diseases/*blood/diagnosis/*drug therapyRisk AssessmentSignal TransductionTreatment Outcome
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PMID: 20177398
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Research group Mécanisme de l'inflammation articulaire (44)
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GABAY, Cem, LAMACCHIA, Céline, PALMER-LOURENCO, Gaby. IL-1 pathways in inflammation and human diseases. In: Nature Reviews Rheumatology, 2010, vol. 6, n° 4, p. 232-241. https://archive-ouverte.unige.ch/unige:20951

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Deposited on : 2012-05-23

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