Total parenteral nutrition (TPN) is frequently used for surgical patients who cannot tolerate enteral feedings. A number of alterations occur in the intestinal mucosa with the administration of TPN, including loss of mucosal barrier function, decline in mucosal epithelial growth, and significant change in the immunologic defense of the host. These changes can lead to transmucosal passage of endotoxin and potentially deadly bacteria which may cause of increased septic complications in patients receiving TPN. Despite recognition of these mucosal changes, little is known regarding the immunologic population of the mucosa, the intraepithelial lymphocytes (IEL), during TPN administration. Because the IEL is in close contact with epithelial cells and produces a number of cytokines which can modulate epithelial function, the investigators examined changes in the IEL using a mouse model of TPN. The preliminary results showed that the IEL undergoes significant phenotypic changes during the administration of TPN, including a significant decline in the CD4+, CD44+ (marker of T-cell maturity) and CD8ab+ (thymic-derived-populations). Functionally, IEL show a significant decline in proliferation. An increased expression of interferon gamma (INF-g) mRNA is noted with TPN. This may explain the epithelial leak associated with TPN, as INF-g can break down an epithelial barrier. This proposal postulates that IEL change during TPN administration, and that these changes may mediate observed increases in epithelial permeability. The proposed research will: expression of regulatory cytokines during TPN administration and correlate these changes with physiologic measurements of mucosal permeability. 3. Determine the mechanism(s) responsible for loss of the thymic-derived portion of the IEL while mice receive TPN. 4. Determine which enteral antigens or nutrients are required for the maintenance of a normal IEL. Information derived from this study will enhance understanding of the mechanisms involved with the development of TPN-associated epithelial leak, increase knowledge of the role that enteral nutrients have in the maintenance of IEL, and may lead to novel approaches in the prevention of the adverse process.
| Ochi, Takanori; Feng, Yongjia; Kitamoto, Sho et al. (2016) Diet-dependent, microbiota-independent regulation of IL-10-producing lamina propria macrophages in the small intestine. Sci Rep 6:27634 |
