Glutamine Prevents Total Parenteral Nutrition-Associated Changes to Intraepithelial Lymphocyte Phenotype and Function: A Potential Mechanism for the Preservation of Epithelial Barrier Function

Abstract

Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.