Inflammasome and IL-1beta-mediated disorders

Abstract

The NLRP3 inflammasome is an intracellular complex that regulates the release of proinflammatory cytokines such as interleukin-1beta in response to exogenous pathogens and endogenous danger signals. Evidence from studies involving human genetics, human ex vivo mononuclear cell responses, and in vivo and in vitro murine models confirms the importance of the inflammasome and interleukin-1beta in the pathogenesis of several inherited and complex diseases. The availability of several effective interleukin-1beta targeted therapies has allowed for successful proof-of-concept studies in several of these disorders. However, many other diseases are likely to be mediated by the inflammasome and interleukin-1beta, providing additional targets in the future.

Fig. 1

The inflammasome. The inflammasome is an intracellular protein complex consisting of NRLP3, apoptosis-associated speck protein with a caspase activation and recruitment domain (ASC), and caspase-1. Pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) activate the inflammasome, resulting in activation of caspase-1 and cleavage of pro-interleukin (IL)-1β to form active IL-1β, which leaves the cell and can then bind to the IL-1 receptor, resulting in inflammation. Several IL-1β targeted therapies have been developed. mAb—monoclonal antibody. Figure design by S. Brydges