Specific inflammasomes in complex diseases

Blocking the cytokines Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18) benefits a diverse range of inflammatory pathologies. In each of these diseases, different cytoplasmic innate immune receptors nucleate individual protein complexes known as inflammasomes, to regulate the production of active IL-1β or IL-18. This review will outline the complex diseases where these cytokines are pathogenic, and explain which inflammasome(s) may be responsible. For example, inflammasomes nucleated by NLRP3 and NLRP6 integrate signals from metabolic and commensal systems contributing to metabolic dysfunction and type 2 diabetes. On the other hand, NLRP1 and AIM2 are more broadly implicated in autoimmunity and allergy. Furthermore, each inflammasome has unique roles in pathogen recognition, which may determine the outcome of polymicrobial infection and link different infectious co-morbidities to chronic inflammatory disease. We can now imagine a time when targeted inflammasome inhibitors will be employed in the clinic, tailoring treatments to particular diseases, and perhaps individual patients.