Lack of enteral nutrition—effects on the intestinal immune system

Abstract

Total parenteral nutrition (TPN) results in a loss of mucosal immune function by alterations in both phenotype and function of intraepithelial lymphocytes (IEL). We hypothesized that the observed changes with TPN administration are caused by the lack of enteral feeding, and not to the TPN solution itself. Mice received oral feeding (Control), TPN alone (TPN), or TPN plus oral feeding (TPN+Food). Mice were killed after 7 days, and bacteriological cultures from spleen, liver, and mesenteric lymph nodes obtained, with bacterial translocation (BT) being defined as a positive culture. IEL phenotype was analyzed by flow cytometry. IEL messenger RNA (mRNA) cytokine expression used reverse transcriptase polymerase chain reaction (RT-PCR). Apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining. BT significantly (P < 0.05, with analysis of variance [ANOVA]) increased in the TPN group (53%) compared with Control (9%) and TPN+Food (14%) groups. TPN also resulted in a significant (P < 0.01) increase in epithelial cell apoptosis: TPN 7.6 +/- 1.1% versus Control 2.9 +/- 1.1% and TPN+Food 2.1 +/- 0.3% (mean +/- SD). Height of the villus-crypt complex was significantly decreased in TPN mice (315 +/- 16 microm) compared with Control (431 +/- 27 microm) and TPN+Food (421 +/- 26 microm) groups. IEL phenotypes significantly changed with TPN administration: CD4+ CD8- as well as CD4+ CD8+ subpopulations were reduced compared with Control or TPN+Food mice; as were the CD8alphabeta+ thymus-dependent, and CD8+ CD44+ mature IEL. IEL cytokine mRNA expression was also significantly altered with TPN: IL-2 and IL-10 expression declined, and IL-4 IL-6, interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta1), and tumor necrosis factor-alpha (TNF-alpha) were increased, when compared with Control or TPN+Food mice. This study demonstrates that the major factor responsible for TPN-induced BT and IEL-changes is the lack of enteral feeding and not the administration of the TPN solution itself.