A Self-Assembled Metabolic Regulator Reprograms Macrophages to Combat Cytokine Storm and Boost Sepsis Immunotherapy.

ABSTRACT: Sepsis, a life-threatening inflammatory disorder characterized by multiorgan failure, arises from a dysregulated immune response to infection. Modulating macrophage polarization has emerged as a promising strategy to control sepsis-associated inflammation. The endogenous metabolite itaconate has shown anti-inflammatory potential by suppressing the stimulator of interferon genes (STING) pathway, but its efficacy is inhibited by hyperactive glycolysis, which sustains macrophage overactivation. Here, we revealed a critical crosstalk between the itaconate-STING axis and glycolysis in macrophage-mediated inflammation. Building on this interplay, we developed a novel nanoparticle LDO (lonidamine disulfide 4-octyl-itaconate), a self-assembled metabolic regulator integrating an itaconate derivativ

SUBMITTER: Zhuang J 

PROVIDER: S-EPMC11959697 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature