Pathogenesis of adult onset Stills disease
An unidentified infectious or environmental trigger provides a specific danger signal (e.g., pathogen-associated and damage-associated molecular patterns) that bind to toll-like receptors on macrophages and neutrophils, leading to activation of specific inflammasomes resulting in caspase activation and overproduction of IL-1β. This cytokine can further contribute to macrophage and neutrophil activation resulting in overproduction of several other proinflammatory cytokines (IL-6, IL-8, IL-17, IL-18, and TNF). Unidentified genetic factors may predispose a person to developing this cytokine storm. Alternatively, regulatory antiinflammatory mechanisms (regulatory T cells, IL-10, etc) may be defective in halting the unrestrained amplification of proinflammatory cytokines.
