Macrophages respond to pathogens and tissue damage via pattern recognition receptors (PRR) that sense pathogen (PAMP) or damage (DAMP) associated molecular patterns. NLRP3, a member of the Nod-like receptor (NLR) family that is induced upon macrophage activation, senses cytosolic oxidized mitochondrial DNA (ox-mtDNA) that is generated when activated macrophages are exposed to NLRP3- activating DAMPs, such as ATP, uric acid, or amyloid β, triggers IL-1β and IL-18 production and release. IL-1β and IL-18 are members of the IL-1 family of cytokines representing two of eleven members. As a whole, the IL-1 group of cytokines can induce strong inflammatory signals. Moreover, IL-1β and IL-18 are unique members because they are inactive until undergoing proteasomal cleavage by caspase-1 leading to the formation of active biological forms. Recent work has shown that NLRP3 inflammasome dependent production of IL-1β and IL-18 is involved in the pathogenesis of many devastating diseases, including cancer, Alzheimer’s disease, rheumatoid diseases and cryopyrin-associated periodic syndromes. and autoimmune diseases such as lupus or Still’s diseases. Thus, there exists a need to modulate the production of both IL-1β and IL-18.