Li et al. discovered that 4-octyl itaconate (4-OI) directly covalently modifies TYK2 and JAK1 to inhibit the type I interferon response. Endogenous metabolite itaconate in sepsis is a JAK inhibitor. In the mouse, in vivo experiments, intraperitoneal injection of 4-octyl itaconate could alleviate multi-organ damage caused by sepsis.