with the unique role of IL-1 in the pathogenesis of autoinflammatory diseases. In this issue of Arthritis & Rheumatism, Joosten et al provide experimental data that causally explain the clinical events that consistently precede flares of gout and assess how these mechanisms are related to the production of IL-1 (3). Despite several reports indicating that the addition of MSU crystals to mononuclear phagocytes induces IL-1 secretion (4,5), the notion that MSU is a sole activator of active IL-1 is inconsistent with the clinical reality of gouty attacks. For example, why do fewer than 10% of individuals with hyperuricemia and deposits of MSU crystals in the joints develop the disease, while the remainder do not? Why do acute flares of gout often occur in the middle of the night? Why do patients receiving antitumor therapies have high uric acid levels but no clinical signs of gout? Why do individuals with hyperuricemia have attacks of gout when they diet and lose weight? Although the associations of food and alcohol consumption with attacks of gout have been known for many centuries, how such lifestyle events are related to IL-1 activity has not been explored. Therefore, those published studies that show that MSU crystals by themselves induce active IL-1 require a careful reevaluation of the evidence to be consistent with the clinical associations of gout attacks. This editorial does not attempt to review the association of gout attacks with the consumption of food and alcohol. Instead, it draws attention to the study by Joosten and coworkers (3), which goes a long way in providing the basis for the production of IL-1 induced by MSU, with the conclusion that more than MSU is needed to trigger an acute attack of gout. First, the results of the Joosten study confirm that pure MSU crystals per se could not induce IL-1 production from primary peripheral blood mononuclear cells (PBMCs) isolated from healthy donors (6), and these observations were extended to mouse peritoneal macrophages. In order to relate the association with dietary intake of fatty foods, free fatty acids (FFAs) of increasing lengths were also added to cultures of human