Although additional studies are required to fully understand the modulation of NLRP3 expression and NLRP3 inflammasome activity by XO and its potential molecular mechanisms, our study describes for the first time that higher concentrations of endogenous CORT are involved in the downregulation of NLRP3 expression and its inflammasome activity in macrophages in vitro and provides a potential target, such as XO, for the modulation of inflammation after surgical injury and in NLRP3-associated diseases, such as autoinflammatory diseases, gout, and diabetes. Here, XDH is linked to diabetes mellitus.