Intravenous Arginine Administration Benefits CD4 + T-Cell Homeostasis and Attenuates Liver Inflammation in Mice with Polymicrobial Sepsis

• Published in: Nutrients Vol. 12; no. 4; p. 1047
• Main Authors: Yeh, Chiu-Li, Tanuseputero, Sharon Angela, Wu, Jin-Ming, Tseng, Yi-Ru, Yang, Po-Jen, Lee, Po-Chu, Yeh, Sung-Ling, Lin, Ming-Tsan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.04.2020; MDPI
• Subjects: Abdomen; Animals; Aorta; arginine; Arginine - administration & dosage; Arginine - pharmacology; Blood circulation; Body weight; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cecum; Disease Models, Animal; Gene expression; Helper cells; Hepatocytes; Homeostasis; Homeostasis - immunology; Infections; Inflammation; Infusions, Parenteral; Inhibitors; Interleukin 17; Intravenous administration; Laboratory animals; Liver; Liver - immunology; liver inflammation; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Male; Mice, Inbred C57BL; Nitric oxide; Nitric Oxide - physiology; Nitric-oxide synthase; Physiology; Plasma; regulatory T cell; Sepsis; Sepsis - drug therapy; Sepsis - immunology; Software; T helper cell; T-Lymphocytes, Regulatory - immunology; United States > US; nitric oxide; liver inflammation; arginine; regulatory T cell; T helper cell; sepsis
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12041047

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4 T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4 T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4 T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4 T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4 T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.