IL-1 Superfamily and Inflammasome

The importance of IL-1 family members to the innate response became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I (IL-1R1) is found in the Toll protein of the fruit fly. Of the 11 members of the IL-1 family, IL-1α, IL-1β, IL-1Ra, and IL-18 have been thoroughly studied in vitro in animal models of disease and in humans. IL-1α is an unusualmember of the IL-1 family because IL-1α is found constitutively in epithelial and mesenchymal cell types of healthy subjects, whereas IL-1β is primarily induced under disease conditions. Following the cDNA cloning of mouse IL-1α in 1984, recombinant IL-1α became available for study in humans with cancer. Regardless of the stimulus, in monocytes and macrophages, specific inhibitors of caspase-1 reduce the secretion of mature IL-1β, while precursor IL-1β accumulates inside the cell. The rate-limiting step in the processing and secretion of IL-1β takes place with activation of the inflammasome.