Objective: Total parenteral nutrition (TPN), with the complete removal of enteral nutrition, results in marked changes in intestinal intraepithelial lymphocyte (IEL) function and phenotype. Previous work shows that TPN results in a loss of intestinal epithelial cell-derived interleukin-7 (IL-7), and this loss may play an important role in development of such TPN-associated IEL changes.
Methods: To further understand this relation, we generated a transgenic mouse (IL-7), which overexpresses IL-7 specifically in intestinal epithelial cells. We hypothesized that this localized overexpression would attenuate many of the observed TPN-associated IEL changes.
Results: Our study showed that TPN administration led to significant changes in IEL phenotype, including a marked decline in the CD8alphabeta+, CD4+, and alphabeta-TCR+ populations. IEL basal proliferation decreased 1.7-fold compared with wild-type TPN mice. TPN administration in wild-type mice resulted in several changes in IEL-derived cytokine expression. IL-7 mice given TPN, however, maintained IEL proliferation, and sustained normal IEL numbers and phenotype.
Conclusions: We conclude that specific intestinal IL-7 overexpression significantly attenuated many IEL changes in phenotype and function after TPN administration. These findings suggest a mechanism by which TPN results in observed IEL changes.