Cell death in sepsis: unveiling new perspectives on organ dysfunction

Despite significant advances in modern intensive care, sepsis remains a life-threatening inflammatory disease worldwide. High mortality is mainly due to multiple organ dysfunction syndrome (MODS). Emerging research has shifted the focus to regulating cell death (RCD) pathways, particularly siderophosis and pyrophosphosis, which are considered major drivers of immune damage. In addition to inducing cell death, these RCD mechanisms exacerbate the inflammatory response, disrupt physiological balance, and directly accelerate MODS-related failure. Key pathogenic mechanisms include gasdermin D (GSDMD)-mediated scorching, cytokine storming, iron destruction-related lipid peroxidation impairment of cardiac function, and immune apoptosis leading to severe immunosuppression. While pharmacologically targeting these pathways has therapeutic potential, striking a balance between efficacy and infection defense remains challenging. Therefore, improving sepsis treatment requires a time-adaptive, multi-target approach. Additionally, identifying reliable biomarkers is crucial for accurate diagnosis, ultimately improving patient outcomes.