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

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.