Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis

• Published in: Nutrients Vol. 14; no. 17; p. 3557
• Main Authors: Yeh, Chiu-Li, Wu, Jin-Ming, Chen, Kuen-Yuan, Wu, Ming-Hsun, Yang, Po-Jen, Lee, Po-Chu, Chen, Po-Da, Yeh, Sung-Ling, Lin, Ming-Tsan
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 29.08.2022; MDPI
• Subjects: 25-Hydroxyvitamin D; Alfacalcidol; Bacterial infections; Calcifediol; Calciferol; Calcitriol; CD4 antigen; CD4 lymphocytes; Cecum; Cell differentiation; cholecalciferol; Clinical outcomes; Clinical trials; Comparative analysis; Complications and side effects; Cytochrome P450; Cytochromes P450; Cytokines; Development and progression; Diet; Diet therapy; Disease; Dosage and administration; Gastrointestinal system; Gene expression; Health aspects; Helper cells; High fat diet; Homeostasis; Ileum; Infection; Inflammation; Inflammatory bowel disease; Interleukin 22; Intestine; Intravenous administration; Laboratory animals; Lipids; Lymph nodes; Lymphocytes; Lymphocytes T; Mucin; Nosocomial infections; Obesity; Peroxides; Physiological aspects; Proteins; regulatory T cell; Sepsis; Small intestine; T cells; T helper cell; tight junction; Tumor necrosis factor-TNF; Vitamin D; Taiwan; California; Lithuania; United States > US
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu14173557

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways.