Sepsis is a complex, multifactorial syndrome characterized by a dysregulated host response to
infection, leading to severe organ dysfunction and high mortality rates among
critically ill patients. Hypovitaminosis C and
vitamin C deficiency are frequently observed in septic patients, prompting interest in the potential therapeutic role of
ascorbic acid. Although
intravenous administration of
ascorbic acid has been investigated in multiple clinical trials for
sepsis treatment, the specific immunomodulatory mechanisms underlying its effects remain elusive. This study aimed to investigate the protective effects of high-dose
ascorbic acid on experimental
sepsis. Results show that
intravenous administration of high-dose
ascorbic acid (250 mg/kg) attenuated
sepsis-induced organ dysfunctions in a cecal
ligation and
puncture (CLP)-induced septic mouse model.
Ascorbic acid improved splenic cell apoptosis and increased the number of CD3+ T cells in septic mice induced by CLP. Furthermore,
ascorbic acid downregulated PD-L1 expression in livers, reduced PD-1 expression in spleens, and inhibited the phosphorylation of STAT1 at Y701 in multiple organs of CLP-induced septic mice. The in vitro experiments also revealed that 800 μM
ascorbic acid suppressed STAT1 phosphorylation and inhibited
lipopolysaccharide (LPS) and IFN-γ-induced PD-L1 expression in macrophages. These findings suggest that
ascorbic acid prevents
sepsis-associated organ dysfunction through the p-STAT1/PD-L1 signaling pathway. Our study provides new insights into the potential
therapeutic use of
ascorbic acid in
sepsis.