Glycyl-L-Glutamine-Enriched Total Parenteral Nutrition Maintains Small Intestine Gut-Associated Lymphoid Tissue and Upper Respiratory Tract Immunity

Background: IV administration of a total parenteral nutrition (TPN) solution results in small intestinal gut-associated lymphoid tissue (GALT) atrophy, lowers small intestinal immunoglobulin A (IgA) levels, and impairs upper respiratory tract secretory IgA-mediated mucosal immunity; isonitrogenous supplementation of TPN with 2% glutamine attenuates these changes. This experiment examines whether a 2% glycyl-L-glutamine-enriched TPN solution reverses IV TPN-induced changes as effectively as L-glutamine. Methods: Male Institute of Cancer Research (ICR) mice underwent intranasal inoculation with H1N1 influenza virus to establish immunity. After 3 weeks, mice were randomized to chow, IV feeding of a TPN solution, glutamine-enriched TPN, or glycyl-L-glutamine-enriched TPN. After 4 days of feeding, mice were challenged intranasally with influenza virus and killed at 40 hours to determine viral shedding from the respiratory tract; normal convalescent mice do not shed virus because they possess intact IgA-mediated mechanisms. Lymphocytes were isolated from Peyer's patches, the intraepithelial layer, and lamina propria to determine cell yields. Results: Total lymphocyte yield in the Peyer's patches, the intraepithelial layer, and lamina propria decreased with TPN but remained normal with glutamine and glycyl-L-glutamine. Upon challenge, 70% of the mice in the TPN group shed virus in nasal secretions, whereas only 20% of the glutamine-treated group, 18% of glycyl-L-glutamine group and none of the Chow group were virus positive. Conclusions: L-Glutamine and glycyl-L-glutamine have similar effects on IV administered TPN-associated (GALT) atrophy and decreased upper respiratory tract immunity. (Journal of Parenteral and Enteral Nutrition 22:31-36, 1998)