Primer: inflammasomes and interleukin 1 beta in inflammatory disorders

Inflammasomes are large, multimeric protein complexes that link the sensing of microbial products and metabolic stress to the proteolytic processing of prointerleukin (pro-IL)-1 beta to its active form. NALP1 and NALP2 are founding members of the Nod-like receptor family. Other Nod-like receptors, including NALP3 and NOD2, which are associated with inflammatory disorders, have also been described. The NALP I and NALP3 inflammasomes are located in the cytoplasm and can, therefore, detect intracellular infection through recognition of microbial pathogen-associated molecular patterns. The inflammasome pathways cooperate with Toll-like receptor pathways to mediate a rapid and appropriate response to pathogens and genotoxic stress. Mutations in both pyrin and NALP3 components of inflammasomes are associated with innate-immune-mediated diseases (familial Mediterranean fever and the 'cryopyrinopathies'), and aberrant IL-1 beta processing has been reported in several autoinflammatory conditions, including Muckle-Wells syndrome, chronic infantile neurologic, cutaneous and articular syndrome/neonatal onset multisystem inflammatory disease, and gout. The effectiveness of IL-1 beta blockade in treating many of these conditions has transformed the understanding and management of these disorders and also highlighted the role of aberrant IL-1 beta signaling in other conditions, such as adult-onset Still's disease and systemic juvenile idiopathic arthritis.