BACKGROUND: Total parenteral nutrition (TPN) is associated with sepsis and loss of immune reactivity. The authors previously have shown that changes in the intestinal mucosal immune system--ie, intraepithelial lymphocytes (IEL)--lead to a loss of epithelial barrier function. This may be a mechanism by which bacteria and toxins endanger individuals receiving TPN. To identify altered IEL gene expression during TPN administration, microarray assays were used.
METHODS: Mice received oral feeding (control) or TPN for 7 days. Small bowel IEL were separated and retained, RNA purified, and microarray assays performed (Affymetrix system, 12,491 genes). Results were expressed as quantile-normalized trimmed-means. Significance equals a greater than 2-fold change (TPN v control), P <.01 (t test) or greater than 3-fold, P <.05.
RESULTS: In the TPN group 88, IEL genes were significantly up regulated and 114 downregulated (v control). Of these genes, 4 were identified to have highest degree of upregulation (FK506-binding protein 5; mannose-binding lectin, metallothionein 1 and 2), 2 were highly downregulated (microsomal epoxide hydrolase 1 and cytochrome P450 1a1). These genes were found to have high potential for immune-modulatory effects.
CONCLUSIONS: The observed alterations in IEL gene expression may have an important role in the altered immune response with TPN and may relate to the increase in sepsis with TPN administration.