Emerging Roles and Possible Therapeutic Applications of Arachidonic Acid Metabolites in Sepsis and Sepsis-Associated Organ Dysfunction

Chengpeng Wang,1,* Xiaoqing Jiang,2,* Yanke Chen,1,* Wenbin Nan,1 Zhenyu Peng1,31Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China; 2Department of Geriatric Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China; 3Department of Emergency Medicine, Guilin Hospital of The Second Xiangya Hospital, Central South University, Guilin, 541002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhenyu Peng, Email pengzhenyu1999@csu.edu.cnAbstract: Sepsis is a life-threatening syndrome characterized by dysregulated immune responses, frequently complicated by multiple organ dysfunction. Despite advances in supportive care, targeted therapies remain lacking, and sepsis remains a considerable global health burden. Increasing evidence indicates that arachidonic acid and its metabolites are critical regulators of inflammation, immune responses, and apoptosis in the pathophysiology of sepsis. Arachidonic acid is metabolized through cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) pathways, generating diverse eicosanoids with distinct effects. Pro-inflammatory mediators such as prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and, in certain contexts, 20-hydroxyeicosatetraenoic acid (20-HETE) may exacerbate vascular leakage, oxidative stress, and organ dysfunction. Recent studies have revealed that dynamic alterations in arachidonic acid metabolism contribute to cardiac, pulmonary, hepatic, and renal injury in sepsis. This review consolidates current understanding of arachidonic acid metabolic pathways and their role in sepsis-induced organ injury. Targeting arachidonic acid metabolism—particularly inhibition of COX/LOX-derived eicosanoids or stabilization of protective epoxyeicosatrienoic acids (EETs)—may offer promising therapeutic strategies. Understanding the context-dependent roles of arachidonic acid metabolites may support future biomarker development, patient stratification, and targeted therapeutic strategies for sepsis and sepsis-associated organ dysfunction.Keywords: arachidonic acid, metabolites, sepsis, organ dysfunction