title: 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.
authors.affiliation: Division of Basic Traumatology, National Defense Medical College Research Institute Tokorozawa, Japan 359-8513. fukatsu@ndmc.ac.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Fukatsu
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Moriya
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Jiro
authors.initials: J
authors.lastname: Omata
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yaguchi
authors.forename: Fumie
authors.initials: F
authors.lastname: Ikezawa
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Hoshio
authors.initials: H
authors.lastname: Hiraide
mesh_terms: D000818:Animals; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D015851:Interleukin-7 / Q000008:administration & dosage* / Q000276:immunology; D007413:Intestinal Mucosa; D007421:Intestine, Small / Q000276:immunology; D008297:Male; D051379:Mice; D010289:Parenteral Nutrition, Total; D010581:Peyer's Patches / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology; D018805:Sepsis / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007071:Immunoglobulin A, Secretory; D015851:Interleukin-7