Interferon-γ regulates immunosuppression in septic mice by promoting the Warburg effect through the PI3K/AKT/mTOR pathway.

Background: The main cause of high mortality from sepsis is that immunosuppression leads to life-threatening organ dysfunction, and reversing immunosuppression is key to sepsis treatment. Interferon γ (IFNγ) is a potential therapy for immunosuppression of sepsis, promoting glycolysis to restore metabolic defects in monocytes, but the mechanism of treatment is unclear.

Methods: To explore the immunotherapeutic mechanism of IFNγ, this study linked the Warburg effect (aerobic glycolysis) to immunotherapy for sepsis and used cecal ligation perforation (CLP) and lipopolysaccharide (LPS) to stimulate dendritic cells (DC) to establish in vivo and in vitro sepsis models, Warburg effect inhibitors (2-DG) and PI3K pathway inhibitors (LY294002) were used to explore the mechanism by which IFNγ regulates immunosuppression in mice with sepsis through the Warburg effect.