High-density lipoprotein: a biomarker and therapeutic target in sepsis

Sepsis is a life-threatening condition that stems from a dysregulated host response to an infection, leading to multi-organ dysfunction and death. Sepsis has a remarkably high global burden and accounts for 20% of all deaths worldwide. Nonetheless, possibilities for treatment are limited mainly to early administration of broad-spectrum antibiotics and providing fluid resuscitation. Innovative strategies that target the excessive inflammatory response while supporting the immune system to clear the infection are highly warranted. It is well-established that sepsis significantly impacts lipoprotein metabolism, leading to a substantial decrease in high-density lipoprotein (HDL) as observed in both experimental and clinical studies. Meanwhile, a high HDL level is associated with better sepsis-related prognosis, indicating that strategies aimed at raising HDL could be beneficial in combating sepsis. In this review, we describe changes in lipoprotein metabolism that occur during sepsis, address the various protective functions of HDL based on its endotoxin-neutralizing, anti-bacterial, anti-inflammatory, and anti-oxidative properties, as well as demonstrate modulation of HDL as a potential therapeutic strategy in sepsis.