O25 – Glutamine Improves Innate Immunity and the Intestinal Barrier Function During Parenteral Nutrition

Author(s):

Rebecca Busch, Xinying Wang, Joseph Pierre, Aaron Heneghan, Kenneth Kudsk, University of Wisconsin Madison

Background: PN patients are at increased risk for infectious complications compared to enteral feeding. Impaired mucosal immunity during PN provides a cogent explanation for part of this vulnerability. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated.

Hypothesis: We hypothesized addition of GLN to PN would improve innate immune function during PN.

Methods: Forty-eight hours following venous cannulation, male ICR mice were randomized to receive chow (n = 10), PN (n = 12), or PN+GLN (2%) (n = 13) daily for 5 days. Small intestine wash fluid and ileum segments were collected for analysis of MUC2 and lysozyme density, and luminal levels of IL-4, IL-10 and IL-13. Tissue was also harvested for use in an ex-vivo intestinal segment culture to assess susceptibility of the tissue to enteroinvasive Escherichia coli.

Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < 0.0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal: P < 0.05 and tissue: P < 0.0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced its expression. IL-4, IL-10 and IL-13 decreased significantly with PN compared with chow, whereas GLN significantly increased these 3 cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < 0.05), while GLN significantly decreased enteroinvasion similar to but not statistically different from chow levels (P < 0.05).

Conclusions: GLN supplemented PN improves innate immunity and resistance to bacterial mucosal invasion that is lost with PN. This work confirms a clinical rationale for providing GLN for the protection of the intestinal mucosa with PN.