Bombesin affects mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice.

BACKGROUND

Our prior studies show that intravenous (IV) total parenteral nutrition (TPN) produces atrophy of the small intestine-related gut-associated lymphoid tissue and significant decreases in intestinal IgA levels, the major system of mucosal immunity. Others have noted increased small intestinal permeability, bacterial adherence and translocation, and decreased IgA levels in TPN-fed animals. Bombesin, a neuropeptide, may play a regulatory role in mucosal immunity. It is not clear whether bombesin attenuates the TPN-associated gut-associated lymphoid tissue atrophy.

OBJECTIVE

To examine the effect of bombesin on gut-associated lymphoid tissue integrity and function during IV TPN feeding.

DESIGN

Randomized animal study.

SETTING

A university laboratory.

MATERIALS AND METHODS

Male ICR mice weighing 25 to 30 g were randomized to chow plus IV saline solution (n = 12), IV TPN (n = 12), or IV TPN plus bombesin (15 micrograms/kg, administered intramuscularly three times a day) (n = 12). Animals were killed after 5 days of receiving the experimental diet. Total small intestinal IgA level was quantified by enzyme-linked immunosorbent assay. Lymphocytes were isolated from Peyer's patches, intraepithelial spaces, and lamina propria and were stained with specific antibodies for B and T cells and for T-cell expression of CD4 and CD8 by flow cytometric analysis. Data were analyzed by analysis of variance.

RESULTS

Bombesin prevented the IV TPN decreases in (1) total cell yield and B-cell yield from the Peyer's patches, intraepithelial spaces, and lamina propria; (2) T-cell yield in the intraepithelial spaces and lamina propria; and (3) small intestinal IgA levels. Bombesin also reversed IV TPN decreases in CD4+ and CD8+ T cells in the intraepithelial spaces and Peyer's patches and prevented the decrease in the CD4/CD8 ratio in the lamina propria.

CONCLUSION

Bombesin prevents the TPN-associated atrophy and dysfunction of gut-associated lymphoid tissue, supporting the concept of close neuroimmunologic interaction.