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Unlocking the therapeutic potential of disulfiram in sepsis: Mechanisms and future directions

Qi Wu1,2,*, Wentao Ji1,*, Xiaoting Zhang1 , Qingshuang Zhang3 , Lulong Bo1

 

1Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China. 2Department of Anesthesiology, 904th Hospital of The Joint Logistics Support Force of the PLA, Wuxi 214044, Jiangsu Province, China. 3Department of Pharmacy, Linyi People’s Hospital, Linyi 276000, Shandong Province, China.

* The authors contribute equally

 

Address correspondence to: Lulong Bo, Faculty of Anesthesiology, Changhai Hospital, Naval Medical University, 168 Changhai Road, Yangpu District, Shanghai 200433, China. Tel: +86-021-31158021; E-mail: bartbo@smmu.edu.cn; Qingshuang Zhang, Department of Pharmacy, Linyi People’s Hospital, 27 Jiefang Road. Linyi 276000, Shandong, China. Tel: +86-13853997538; E-mail: zqs0417@163.


DOI: https://doi.org/10.61189/588589vgwoub

 

Received December 10, 2024; Accepted March 4, 2025; Published September 30, 2025


Highlights

● Disulfiram modulates sepsis through multiple mechanisms, potentially reducing excessive inflammation and improving patient outcomes.

● The immunomodulatory effects of disulfiram are complex, influencing inflammatory mediators and immune cell function, thereby restoring immune homeostasis.

● Translating preclinical findings into clinical practice is challenging. Rigorous clinical trials and a more comprehensive understanding of the pharmacokinetics and adverse effects of disulfiram are essential.

Abstract

The leading cause of mortality within ICUs is sepsis; however, treatment options typically fail to appropriately regulate the severely dysregulated host response to this syndrome. Recently, there has been an unexpected observation that the common alcoholic aversion treatment disulfiram has exhibited additional immune-regulatory capabilities outside of its original purpose. Disulfiram has shown some effectiveness in preclinical settings at reducing pyroptosis as well as NLRP3 inflammasome activation. Currently there is no sound systematic evidence that supports the repositioning of disulfiram for use in sepsis; more importantly, significant deficiencies in the current research were also observed and deficiencies with respect to existing investigations indicated that future studies should adopt more precise clinical approaches in order to validate the therapeutic effect of disulfiram against sepsis. Integrating the existing evidence and bringing forward feasible directions for future research also constitutes another goal of this review, which helps us better highlight the value of disulfiram as a treatment in sepsis management and further streamline research and clinical translation efforts for the development of this topic in the near future.

Keywords: Sepsis, disulfiram, inflammation, cell death, signaling pathways

Cite

Wu Q, Ji WT, Zhang XT, Zhang QS, Bo LL. Unlocking the therapeutic potential of disulfiram in sepsis: Mechanisms and future directions. Perioper Precis Med. 2025 Sep; 3 (3): 92-104. doi: 10.61189/588589vgwoub.

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