Lactylation modification - a bridge between sepsis and macrophage metabolic reprogramming

Sepsis is a life-threatening organ failure syndrome triggered by dysregulated host responses to infection. During disease progression, macrophages drive initial hyperinflammatory responses and critically regulate the subsequent immunosuppressive phase. Emerging evidence reveals that macrophage phenotypes dynamically adapt through metabolic reprogramming, creating phenotype-metabolism interdependence. Notably, lactate—long considered merely a glycolytic byproduct—now emerges as a key regulator through histone lactylation. This epigenetic modification fine-tunes macrophage functionality and corrects inflammatory imbalance in sepsis. This breakthrough illuminates lactylation’s central role in macrophage regulation, opening new diagnostic and therapeutic avenues. This review comprehensively examines lactylation mechanisms and their impact on metabolic control in sepsis-associated macrophages.