Autoinflammatory Diseases: Consequences of Uncontrolled Inflammasome Activation

Abstract

Inflammasomes are sensors within the innate immune system that are responsible for the regulation of caspase-1 activation and the initiation of inflammatory responses following cellular infection or damage. A significant number of chronic inflammatory and metabolic diseases have recently been identified to have inflammasome-mediated inflammation as a key driver of their pathogenesis; this area of research is under intense investigation at present. This review focusses on autoinflammatory diseases (AD), a rapidly expanding group of debilitating diseases that are associated with severe systemic inflammation. AD commonly arise as a result of mutations to genes that encode inflammasome components. Monogenic AD are relatively rare because they require fully penetrating mutations; however, they often present at birth and last a lifetime. Clinical awareness of AD is lacking and it is believed that, at present, many cases go undiagnosed. This review specifically discusses a number of inflammasome-associated AD and metabolic disorders that provide significant insight into our understanding of inflammasome signalling pathways. These AD highlight the potency of inflammasomes in their ability to initiate and sustain systemic inflammation. The debilitating symptoms of AD also reveal the extensive consequences of uncontrolled inflammasome activity. Clinical therapies that target the inflammasome and interleukin-1β, a product of its activation, in the successful management of AD and certain metabolic diseases will also be discussed.