Glycyl-L-glutamine-enriched total parenteral nutrition maintains small intestine gut-associated lymphoid tissue and upper respiratory tract immunity.

Abstract

i.v. 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 i.v. TPN-induced changes as effectively as L-glutamine. 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, i.v. 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. 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. L-Glutamine and glycyl-L-glutamine have similar effects on i.v. administered TPN-associated (GALT) atrophy and decreased upper respiratory tract immunity.