Abstract
Sepsis acts as the leading cause of mortality in intensive care units, characterized by life-threatening organ dysfunction due to a dysregulated host response to infection. Vitamin D (VD) pleiotropic functions were demonstrated in different biological processes, including inflammation and immunity. VD receptor (VDR) is a member of the nuclear receptor superfamily, involved in immunoregulation and resistance to infections. Previous studies have demonstrated that VD deficiency is a potential risk factor for sepsis development, which may be regulated by VDR-related physiological processes. In this review, we present a comprehensive overview of the roles of VD and VDR in sepsis, focusing on immune modulation, anti-inflammatory and anti-infective responses, oxidative stress regulation, gut microbiome enhancement, vascular endothelial cell modulation, and antiplatelet activity. We also discuss recent advances in clinical research on VD/VDR in sepsis, considering the clinical implications and potential interventions of VD analogs and VDR ligands in treatment. Despite its challenges, VD holds potential for personalized sepsis interventions. Additionally, VD/VDR may serve as a promising bidirectional immunomodulator, capable of addressing both hyperinflammatory and immunosuppressive phases of sepsis, yet require systematic investigations into its dynamic states and functions across different sepsis phases. Ongoing study and evidence-based guidelines are crucial to maximize its therapeutic benefits and improve clinical outcomes.