Qiqi Wu,* Siyuan Qi,* Zhaofeng Kang, Xiangjun Bai, Zhanfei Li, Jing Cheng, Xijie Dong

Trauma Center/Department of Emergency and Traumatic Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jing Cheng, Email jingcheng@tjh.tjmu.edu.cn Xijie Dong, Email dr.dongxijie@hotmail.com

Abstract: The pathogenesis of sepsis is intricately linked to regulated cell death. As a novel form of regulated cell death, PANoptosis plays a critical role in driving the inflammatory response, impairing immune cell function, and contributing to multi-organ dysfunction in sepsis. This review explores the molecular mechanisms underlying PANoptosis and its involvement in sepsis. By activating multiple pathways, PANoptosis promotes the release of inflammatory cytokines, triggering a cytokine storm that disrupts immune cell homeostasis and exacerbates organ damage. Emerging therapeutic strategies targeting PANoptosis, including chemotherapeutic agents and herbal remedies, are showing potential for clinical application. The concept of targeting PANoptosis offers a promising avenue for developing innovative treatments for sepsis.

Keywords: PANoptosis, regulated cell death, sepsis, therapeutic target