title: 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-βand 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.
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yu-Lei
authors.identifier: 0000-0003-3099-2963
authors.initials: YL
authors.lastname: Gao
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Bin
authors.identifier: 0000-0002-4164-2785
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Jian-Hua
authors.identifier: 0000-0002-7282-2981
authors.initials: JH
authors.lastname: Zhai
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yan-Cun
authors.identifier: 0000-0003-1164-7427
authors.initials: YC
authors.lastname: Liu
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Hai-Xia
authors.identifier: 0000-0003-4565-3833
authors.initials: HX
authors.lastname: Qi
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Ying
authors.identifier: 0000-0002-0715-5617
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Yan-Fen
authors.initials: YF
authors.lastname: Chai
authors.affiliation: Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Song-Tao
authors.identifier: 0000-0003-2244-3497
authors.initials: ST
authors.lastname: Shou
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D050544:L-Gulonolactone Oxidase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009102:Multiple Organ Failure / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D060908:CTLA-4 Antigen; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid