The inflammasome and IL-1β: implications for the treatment of inflammatory diseases

Abstract

The bioactive form of IL-1β, a key immunoregulatory and proinflammatory cytokine, is produced by the inflammasome – a caspase-1 activating molecular platform – in response to selected danger-associated molecular patterns and pathogen-associated molecular patterns. Advances in understanding the role of IL-1β in inflammatory conditions has resulted in IL-1β becoming a therapeutic target for a number of inflammatory diseases beyond the rare monogenic autoinflammatory diseases characterized by aberrant inflammasome function and enhanced bioactive IL-1β production. In the monogenic autoinflammatory diseases known as cryopyrin-associated periodic syndromes, neutralization of IL-1β results in a rapid and sustained reduction in disease severity without severe side effects, which has consequently driven off-label applications of IL-1β-targeted therapy in other inflammatory diseases. This review summarizes inflammatory diseases for which accumulating evidence suggests a therapeutic potential for IL-1β antagonists.