Targeting IL-1β in disease; the expanding role of NLRP3 inflammasome |
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Authors: | Ioannis Mitroulis Panagiotis Skendros Konstantinos Ritis |
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Affiliation: | 1. Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil;2. Post-graduation Program in Endocrinology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil;1. Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, India;2. Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, India;3. School of Pharmacy and Pharmacology, MHIQ, QUM Network, Griffith University, Queensland, Australia |
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Abstract: | NLRP3 inflammasome activation and IL-1β secretion have recently emerged as a central mechanism in the pathogenesis of disease. Genetically defined syndromes like cryopyrin-associated periodic syndromes (CAPS, cryopyrinopathies) and familial Mediterranean fever (FMF) or diseases associated with NLRP3 activation by danger signals like gout, pseudogout, Alzheimer's disease or type 2 diabetes are included in this group of diseases. The contribution of anakinra, a recombinant, nonglycosylated human IL-1 receptor antagonist, in both the identification and treatment of such syndromes was considerable. Recently, rilonacept, a long-acting IL-1 receptor fusion protein, and canakinumab, a fully humanized anti-IL-1β monoclonal antibody, have been developed, with the intention to further extent IL-1β inhibition treatment strategies to a broader spectrum of disorders beyond the characterized autoinflammatory syndromes, offering a more favorable administration profile. On the other hand, the developed caspase-1 inhibitors, even though effective in experimental models, were not proven efficient in the treatment of inflammatory diseases. |
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