Scott W. Canna, MD, Associate Professor of Pediatrics – University of Pennsylvania Perelman School of Medicine, Attending Physician, Pediatric Rheumatology and Immune Dysregulation, Children’s Hospital of Philadelphia
The inflammasome is and innate immune protein complex that assembles in response to cytosolic danger sensing. A variety of triggers, sensors, and nucleator-proteins converge on the activation and export of IL-1b, IL-18, and a variety of intracellular damage-associated proteins. Inflammasome gene mutations are among the best-studied autoinflammatory diseases, and the successful use of IL-1b blockers in these diseases has paved the way for blocking this cytokine in other inflammatory contexts. Herein, we trace the co-evolving biology of the inflammasome and the variety of monogenic diseases associated with its hyperactivity. Along the way, we will contrast the biology of IL-1b and IL-18 and show how this biology may help explain the few but notable genetic diseases associated with great excess of IL-18 and the more common disorders that may respond to IL-18 blockade.