Targeting IL-1beta in disease; the expanding role of NLRP3 inflammasome.
NLRP3 inflammasome activation and IL-1beta 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-1beta monoclonal antibody, have been developed, with the intention to further extent IL-1beta 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.
Mitroulis
Ioannis
I
First Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
Skendros
Panagiotis
P
Ritis
Konstantinos
K
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human