The dual pathogenic role of IL-24 in sepsis: Coupling bacterial dissemination with inflammatory amplification as a therapeutic target.

An overactivated cytokine storm during the early phase of sepsis is associated with increased mortality. Although various cytokine-targeting therapeutic strategies have been evaluated in clinical trials, their efficacy remains limited. Here, we focus on the previously less studied cytokine interleukin-24 (IL-24) and demonstrate its pathogenic role in Escherichia coli (E. coli)-induced sepsis. Elevated IL-24 expression was observed in septic wild-type mice. In contrast, IL-24-/- knockout mice exhibited improved survival, reduced bacterial load, and diminished neutrophil and T-cell infiltration. Both in vitro and in vivo experiments revealed that recombinant IL-24 protein enhances the bacterial accumulation and leukocyte chemotaxis. Finally, inhibition of IL-24 expression significantly reduced sepsis-associated mortality. These findings suggest that IL-24 contributes to sepsis pathogenesis by promoting bacterial dissemination and inflammatory amplification, and identify IL-24 as a potential therapeutic target for the precise treatment of sepsis.