Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential

Sepsis is a severe threat to human health with high mortality rates, but so far its pathogenesis is unclear and lacks effective therapeutic drugs. Macrophages function as one of the most important innate immune cells and play an integral role in the sepsis inflammatory process. Recently, studies have shown that its immune function is associated with the Warburg effect. The Warburg effect refers to the preferential metabolism of glucose to lactate by cells through aerobic glycolysis even with abundant oxygen. It has shown that increasing aerobic glycolysis promotes M1 polarization of macrophages to facilitate inflammation, whereas decreasing aerobic glycolysis can lead to M2 polarization and alleviated inflammation. Interestingly, it was demonstrated that not only does glycolysis affect inflammation, but inflammation in sepsis in turn affects glycolysis. Currently, there is no comprehensive review regarding this issue. Therefore, our review focuses on the mechanisms of the interaction between inflammation and macrophage glycolysis in sepsis. We will address both how inflammatory molecules affect the process of glycolysis in septic macrophages and how glycolytic enzymes and related metabolites contribute to inflammation. We also discuss the potential in targeting glycolysis for the treatment of sepsis. We hope to bring a new perspective to clinical practice.