Background

: Sepsis is a lethal clinical syndrome with T-cell dysregulation, imbalanced inflammatory reactions, and gastrointestinal dysfunction. Obesity coexistent with sepsis can cause more-deleterious disease outcomes. Vitamin D is a nutrient with immunomodulatory property, and it helps maintain the intestinal homeostasis. This study investigated treatment with calcitriol on mesenteric lymph node (MLN) CD4+ T cell polarization and intestinal injury in obese mice with sepsis.

Methods

: A high-fat diet was provided to mice for 10 weeks, and then mice were separated into an OB group without sepsis and sepsis groups which underwent cecal ligation and puncture (CLP). Septic mice were subdivided into groups that were injected with either saline (SS) or calcitriol (SD) via a tail vein 1 h after CLP. Obese mice with sepsis were sacrificed at 12 or 24 h post-CLP.

Results

: Sepsis resulted in increased percentages of type 2 T helper (Th2), Th17, and regulatory T (Treg) cells in MLNs. Also, inflammation-associated genes were upregulated, while tight junction genes were downregulated in the intestines after CLP. Compared to the SS group, the SD group exhibited reduced Th2, Th17, and Treg percentages in MLNs. Also, intestinal inflammatory chemokine expressions were reduced, while MUC2, ZO-1, and occludin had increased after CLP. Lower inflammatory cytokine levels in peritoneal lavage fluid in the ileum were also noted in the SD group.

Conclusions

: Intravenous calcitriol treatment after sepsis can elicit more-balanced CD4 T cell subsets in lymph nodes near the intestines and alleviate intestinal inflammation and injury in obese mice complicated with sepsis.

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