The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression

Abstract

Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.

Dietary Intake of Ascorbic Acid Attenuates Lipopolysaccharide-Induced Sepsis and Septic Inflammation in ODS Rats

“…Subsequently, Fisher et al (21) also showed that intraperitoneal injection of AsA in AsA-deficient knockout mice (Gulo2/2 mice), which are unable to synthesize AsA, suppressed injuries to the lung, kidney, and liver produced during sepsis caused by fecal stem solution. Recently, another group (22) reported that parenteral AsA attenuated the symptoms of sepsis and inhibited the immunosuppression of regulatory T cells in Gulo2/2 mice with cecal ligation and puncture. As a noteworthy result, a human phase I trial showed that intravenous AsA infusion reduced the severe organ failures in septic patients (16).…”

Vitamin C and Immune Function

“…Recent research in wild-type and Gulo knockout mice indicated that parenteral administration of 200 mg/kg vitamin C modulated the immunosuppression of regulatory T-cells (Tregs) observed in sepsis [ 89 ]. Vitamin C administration enhanced Treg proliferation and inhibited the negative immunoregulation of Tregs by inhibiting the expression of specific transcription factors, antigens, and cytokines [ 89 ]. The mechanisms involved likely rely on the gene regulatory effects of vitamin C [ 79 , 89 , 199 , 200 ].…”

Overview of the possible role of vitamin C in management of COVID-19

“…Moreover, vitamin C supplement of 200 mg/day for 1–3 months increased IgG and IgM serum levels and improved humoral immune response in elderly [ 43 ]. An animal study showed that vitamin C inhibited the negative immunoregulatory effect of T regulatory cells, which in turn enhanced T cell-medicated response leading to improvement of sepsis and sepsis-induced multi-organ failure [ 11 ]. Vitamin C modulates the release of various inflammatory mediators.…”

“…Sepsis leads to cellular immunosuppression. Treatment of mice with high dose (200 mg/kg) of IV vitamin C inhibited the negative immunoregulatory effect of T regulatory cells, which in turn enhanced T cell-mediated cellular immune response, and resulted in improvement of sepsis and sepsis-induced multi-organ dysfunction syndrome [ 11 ]. Therefore, vitamin C could be beneficial as a supportive treatment of sepsis and septic shock, which are common complications associated with COVID-19.…”