Gene alteration of intestinal intraepithelial lymphocytes with administration of total parenteral nutrition

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. (C) 2003 Elsevier Inc. All rights reserved.