Recovery of gut-associated lymphoid tissue and upper respiratory tract immunity after parenteral nutrition

Abstract

Objective: The authors characterize the recovery of parenteral nutrition-induced changes in gut-associated lymphoid tissue (GALT) and upper respiratory tract immunity with enteral nutrition and provide further information defining the effects of enteral feeding on mucosal immunity.

Summary background data: The small intestine plays a prominent role in development and maintenance of mucosal immunity, both intestinal and extraintestinal, primarily through immunoglobulin A (IgA)-mediated mechanisms. Prior research has shown that mice fed total parenteral nutrition (TPN) have reduced GALT T and B cells, the cells responsible for IgA production, as well as impaired upper respiratory tract immunity to viral challenge of previously immunized animals. The recovery of TPN-induced changes in GALT and upper respiratory tract immunity after enteral refeeding is studied.

Methods: Male institute of Cancer Research mice received 5 days of TPN followed by 0 to 4 days of chow. Small intestinal GALT was characterized by flow cytometry. In a second experiment, animals were immunized intranasally with moused-adapted influenza virus. Three weeks later, one group received a 5-day course of TPN followed by enteral refeeding for 5 days. A second group received TPN alone. Both groups were challenged with intranasal virus and killed 40 hours postchallenge to determine viral shedding from the upper respiratory tract.

Results: Animals fed TPN only had significantly fewer GALT lymphocytes compared with those chow-fed control subjects. Peyer's patch counts increased after a single day of refeeding, returning to normal levels by 48 hours. Lamina propria counts remained significantly depressed after 24 hours of refeeding, but also returned to normal after 48 hours of refeeding. The T-cell and B-cell populations mimicked total cell patterns. Lamina propria CD4+/CD8+ ratio returned to normal only after 72 hours of refeeding. None of the 9 animals refed enterally for 5 days were positive for viral shedding, compared with 8 of 12 matched TPN-fed animals.

Conclusions: Enteral refeeding after TPN is associated with rapid repletion of GALT cellularity, initially within Peyer's patches and subsequently within the lamina propria. Refeeding corrects the impairment of IgA-mediated upper respiratory tract antiviral immunity occurring with TPN administration. This work further enhances the authors' knowledge of the underlying immunologic differences influenced by routes of nutrition.