Exogenous Interleukin 7 Affects Gut-Associated Lymphoid Tissue in Mice Receiving Total Parenteral Nutrition

Abstract

In the absence of enteral nutrient delivery, gut-associated lymphoid tissue (GALT) mass and function are reduced. The purpose of this study was to examine whether exogenous interleukin (IL)-7 treatment reverses intravenous (IV)-total parenteral nutrition (TPN)-induced changes in GALT, immunoglobulin (Ig) A levels, and gut barrier function. Eighty-nine mice were randomized to chow, TPN, or TPN + IL-7 (1 microg/kg, administered IV twice a day) and treated for 5 days. The entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). Small intestinal and bronchoalveolar IgA levels were measured. Proximal and distal small intestinal levels of IgA-stimulating (IL-10) and IgA-inhibiting (IFNgamma) cytokines were determined with enzyme-linked immunoabsorbant assay. Moreover, 1 x 10 live Pseudomonas aeruginosa were delivered by gavage and survival was observed. TPN decreased total cell yields from PPs, IE spaces, and the LP compared with the chow group. IL-7 treatment restored cell numbers. PP CD4+, PP CD8+, IE gammadeltaTCR+, and LP CD4+ cell numbers were higher in the TPN + IL-7 group than in the TPN group. Secretory IgA levels were lower in the TPN and TPN + IL-7 than in the chow group. In the distal small intestine, IFNgamma levels were similar in the three groups, whereas IL-10 levels were reduced in the TPN and TPN + IL-7 groups relative to the chow group. Survival times were reduced in the TPN compared with the chow group, but IL-7 treatment significantly improved survival. Thus, exogenous IL-7 does not improve secretory IgA levels, nor are there any remarkable effects on levels of gut IgA-mediating cytokines. However, IL-7 treatment during TPN reverses TPN-induced GALT atrophy and improves survival in a gut-derived sepsis model.

Effects of Adding Butyric Acid to PN on Gut‐Associated Lymphoid Tissue and Mucosal Immunoglobulin A Levels

“…Lack of a direct nutrition supply from the intestinal lumen to the mucosa, absence of a GLN supply, changes in intestinal commensal bacteria, decreased neuropeptide release, and reduced IL-7 production by intestinal epithelial cells have all been suggested as important factors influencing GALT. [11][12][13][14][15][16]41 Therefore, it is not surprising that butyric acid supplementation does not completely reverse the GALT changes developing in the absence of enteral feeding. However, it is surprising that just a small alteration in the SCFA composition of PN solution significantly improved PP-cell numbers and mucosal IgA levels.…”

“…Although glutamine (GLN) supplementation of PN, neuropeptides, and interleukin 7 (IL-7) intravenous (IV) injection have been regarded as possible surrogates for EN in animal experimental models, [11][12][13][14][15][16] these therapies are far from clinical application, with the exception of GLN supplementation of PN.…”

Influence of Adding Pyrroloquinoline Quinone to Parenteral Nutrition on Gut‐Associated Lymphoid Tissue

“…As previous reports have demonstrated, lack of glutamine in PN solutions, less secretion of neuropeptides and IL-7 during PN, and other factors contribute to impairment of gut immunity. [42][43][44][45][46][47] The present study may add another important piece of knowledge-that PQQ is an important factor for the maintenance of gut immunity. We believe that the present results provide an important clue for developing a new PN formula preserving gut and systemic mucosal immunity.…”

Peptide YY induces enterocyte proliferation in a rat model with total enteral nutrition after distal bowel resection

“…After surgery, all catheterized rats were given a 0.9% NaCl solution, 4.8 ml/day, and were allowed ad libitum access to rat chow and water for 48 h for recovery from surgical stress [14]. During days 2-14 postoperatively, all rats received isocaloric TEN solutions (250 kcal/kg per day) from the free swivel device using an infusion pump.…”