Intravenous arginine administration benefits CD4+ T-cell homeostasis and attenuates liver inflammation in mice with polymicrobial sepsis
Journal
Nutrients
Journal Volume
12
Journal Issue
4
Pages
1047
Date Issued
2020
Author(s)
Abstract
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. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
alanine aminotransferase; amino acid; arginine; aspartate aminotransferase; biochemical marker; citrulline; galectin 3; inducible nitric oxide synthase; interleukin 17; interleukin 1beta; interleukin 4; interleukin 6; lipid peroxide; malonaldehyde; nitric oxide; nitric oxide synthase inhibitor; thiobarbituric acid reactive substance; tumor necrosis factor; arginine; nitric oxide; amino acid blood level; animal cell; animal experiment; animal model; animal tissue; Article; CD4+ T lymphocyte; cecal ligation and puncture-induced sepsis; cell subpopulation; controlled study; flow cytometry; gene expression; gene expression level; hepatitis; homeostasis; homeostasis and regulation; male; mouse; mRNA expression level; multiple reaction monitoring; nonhuman; paraaortic lymph node; polarization; real time polymerase chain reaction; regulatory T lymphocyte; RNA extraction; single drug dose; Th1 cell; Th1 Th2 balance; Th17 cell; ultra performance liquid chromatography; upregulation; animal; C57BL mouse; CD4+ T lymphocyte; disease model; homeostasis; immunology; inflammation; liver; parenteral drug administration; physiology; sepsis; Animals; Arginine; CD4-Positive T-Lymphocytes; Disease Models, Animal; Homeostasis; Inflammation; Infusions, Parenteral; Liver; Male; Mice, Inbred C57BL; Nitric Oxide; Sepsis; T-Lymphocytes, Regulatory
Type
journal article