High-dose ascorbic acid potentiates immune modulation through STAT1 phosphorylation inhibition and negative regulation of PD-L1 in experimental sepsis

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 i nsights into the potential therapeutic use of ascorbic acid in sepsis.Graphical abstract
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research