Individual neuropeptides regulate gut-associated lymphoid tissue integrity, intestinal immunoglobulin A levels, and respiratory antibacterial immunity

Background: Total parenteral nutrition (TPN) leads to atrophy of the gut-as sociated lymphoid tissue (GALT) and a significant decrease in intestinal im munoglobulin A (IgA) levels, a major constituent of mucosal immunity. Bombe sin (BBS) prevents TPN-induced GALT atrophy and maintains intestinal IgA le vels. BBS, a neuropeptide analogous to gastrin-releasing peptide in humans, stimulates the release of other gut neuropeptides including cholecystokini n (CCK), gastrin, and neurotensin (NT). This study investigates the ability of CCK, gastrin, or NT to individually prevent TPN-induced GALT atrophy an d preserve respiratory immunity. Methods: Experiment 1: Male mice were rand omly assigned to receive chow, TPN, TPN plus CCK, TPN plus gastrin, or TPN plus NT. After 5 days of feeding, Peyer's patches (PP) from the proximal an d distal small bowel were harvested and analyzed for cell yields. PP cells were also analyzed for GALT cell type. Small bowel IgA levels were measured by enzyme-linked immunosorbent assay (ELISA). Experiment 2: Mice were rand omly assigned to receive either liposomes containing Pseudomonas antigen or liposomes without antigen. After 10 days, mice were randomly assigned to t he same five treatment groups, fed for 5 days, and then given intratracheal Pseudomonas. Mortality was assessed after 48 hours. Results: Experiment 1: GALT cell reductions due to TV-TPN were greater in the distal than proxima l small bowel. All three neuropeptides prevented most TPN-induced GALT atro phy due mainly to the maintenance of the B-cell and T-cell populations in t he PP of the distal bowel. Intestinal IgA levels were significantly higher in the animals treated with neuropeptides than animals treated with TPN onl y; however, these IgA levels were not maintained at levels observed in chow -fed animals. Experiment 2: Immunization resulted in significantly lower mo rtality in animals fed chow, TPN plus CCK, and TPN plus gastrin. TPN alone and TPN plus NT resulted in loss of immunity and mortality rate at comparab le levels to unimmunized animals. Conclusions: Supplementation of TV-TPN wi th CCK, gastrin, and NT prevents GALT atrophy, primarily in the distal bowe l. Intestinal IgA levels improve but not to normal levels. CCK and gastrin reversed IV-TPN-induced effects on antibacterial pneumonia in immunized ani mals while NT did not.