Sphingomyelin Liposomes Ameliorate Lipopolysaccharide-Induced Sepsis via Extracellular Vesicle-Mediated Exocytosis of Lipopolysaccharide

Sepsis remains a leading cause of death worldwide, and treatment options are limited. Antivirulence strategies that target toxins have emerged as a promising next-generation therapeutic approach due to the potential shown in preclinical studies. Here, we present the efficacy of sphingomyelin (SM) liposomes in modulating inflammatory responses and inhibiting disease progression in lipopolysaccharide (LPS)-induced sepsis. Our findings demonstrate that SM liposomes promote the exocytosis of LPS from LPS-challenged macrophages by enhancing the secretion of extracellular vesicles (EVs). SM liposomes further reduce the production of pro-inflammatory cytokines in LPS-challenged macrophages through EV-mediated LPS exocytosis. In an LPS-induced sepsis mouse model, we show that the systemic administration of SM liposomes significantly reduces local and systemic inflammation, improving the survival rate of mice. Our results illustrate the potential of SM liposomes as an antivirulence agent for the treatment of bacterial infections and sepsis.