Bombesin affects mucosal immunity and gut-associated lymphoid tissue in intravenously fed mice
J. Li, K. A. Kudsk, M. Hamidian and B. L. Gocinski
Department of Surgery, University of Tennessee, Memphis, USA.
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.