Abstract
A growing number of systemic hereditary inflammatory diseases characterized by periodic fevers and elevated acute-phase proteins during flares has been linked to deregulated inflammasome function and excessive bioactivity of interleukin (IL)-1. All these conditions respond, at varying degrees, to the specific blockade of IL-1. The remarkable progress with IL-1 antagonists in treating hereditary inflammasome-based disorders has offered new hope for several patients with further non-hereditary autoinflammatory conditions from multifactorial backgrounds. The effectiveness of the IL-1 blockade has transformed our understanding and management of many complex diseases and highlighted the role of aberrant IL-1 signaling in enigmatic conditions, characterized by recurrent or continuous inflammation and a lack of a role for autoreactive T-cells or autoantibody production. To date, the long-term blockade of IL-1 has been found to restore the clinical equilibrium in systemic inflammasomopathies of childhood, and IL-1 inhibitors have become cardinal weapons in managing both monogenic innate immunity defects and a plethora of polygenic diseases occurring in children, including Still's disease, Kawasaki disease, recurrent pericarditis, chronic non-bacterial osteomyelitis, and Behçet's disease. Very few side effects have been reported with the long-term use of anakinra, rilonacept, or canakinumab, and their safety profile has been largely documented even in childhood. Further investigations into the role of inflammasomes in the pathogenesis of autoimmune conditions as well as brain degenerative or cardiovascular disorders can be expected, paving the way for precision medicine with benefits beyond inhibiting signaling by individual IL-1-family cytokines.