Effect of glutamine-enriched total parenteral nutrition on small intestinal gut-associated lymphoid tissue and upper respiratory tract immunity

Abstract

Background: Our prior work shows that total parenteral nutrition (TPN) causes small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small intestinal immunoglobulin A (IgA) levels, and impairs secretory IgA-mediated mucosal immunity of the upper respiratory tract. These experiments examine whether an isonitrogenous 2% glutamine-enriched TPN solution prevents these changes.

Methods: Institute of Cancer Research mice were randomized to chow (chow), intravenous feeding of a TPN solution (TPN), or glutamine-enriched TPN (glutamine) groups. After mice were fed for 5 days, lymphocytes were isolated from Peyer's patches, the intraepithelial layer, and lamina propria to determine cell yields and phenotypes. Total small intestinal IgA levels were analyzed by means of enzyme-linked immunosorbent assay. In a second series of experiments, mice underwent intranasal inoculation with H1N1 virus to establish immunity. After 3 weeks mice were randomized to chow, TPN, or glutamine groups. After feeding for 5 days, mice were rechallenged with intranasal virus and killed at 40 hours to determine viral shedding from the upper respiratory tract.

Results: Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and lamina propria, small intestinal IgA levels, and the CD4+/CD8+ ratio in the lamina propria decreased with TPN but remained normal with glutamine. On rechallenge, 87% of the mice in the TPN group shed virus in nasal secretions, whereas only 38% of the glutamine-treated group (p < 0.05 versus TPN) and 7.1% of the chow group (p < 0.002 versus TPN) were virus positive.

Conclusions: Isonitrogenous supplementation of TPN with 2% glutamine improves IgA-mediated protection in the upper respiratory tract and normalizes GALT populations.