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Interleukin‐7 Dose‐Dependently Restores Parenteral Nutrition–Induced Gut‐Associated Lymphoid Tissue Cell Loss but Does Not Improve Intestinal Immunoglobulin A Levels
Author(s) -
Fukatsu Kazuhiko,
Moriya Tomoyuki,
Ikezawa Fumie,
Maeshima Yoshinori,
Omata Jiro,
Yaguchi Yoshihisa,
Okamoto Koichi,
Mochizuki Hidetaka,
Hiraide Hoshio,
Hardy Gil
Publication year - 2006
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607106030005388
Subject(s) - intraepithelial lymphocyte , parenteral nutrition , lamina propria , enteral administration , cd8 , immunoglobulin a , lymphatic system , medicine , intestinal mucosa , gut associated lymphoid tissue , t cell , biology , endocrinology , antibody , immune system , immunology , immunoglobulin g , pathology , epithelium
Background: Without enteral nutrition, the mass and function of gut‐associated lymphoid tissue (GALT), a center of systemic mucosal immunity, are reduced. Therefore, new therapeutic methods, designed to preserve mucosal immunity during parenteral nutrition (PN), are needed. Our recent study revealed that exogenous interleukin‐7 (IL‐7; 1 μg/kg twice a day) restores the GALT cell mass lost during intravenous (IV) PN but does not improve secretory immunoglobulin A (IgA) levels. Herein, we studied the IL‐7 dose response to determine the optimal IL‐7 dose for recovery of GALT mass and function during IV PN. We hypothesized that a high dose of IL‐7 would increase intestinal IgA levels, as well as GALT cell numbers. Methods: Male mice (n = 42) were randomized to chow, IL‐7‐0, IL‐7‐0.1, IL‐7‐0.33, IL‐7‐1 and IL‐7‐3.3 groups and underwent jugular vein catheter insertion. The IL‐7 groups were fed a standard PN solution and received IV injections of normal saline (IL‐7‐0), 0.1, 0.33, 1, or 3.3 μg/kg of IL‐7 twice a day. The chow group was fed chow ad libitum . After 5 days of treatment, the entire small intestine was harvested and lymphocytes were isolated from Peyer's patches (PPs), intraepithelial (IE) spaces, and the lamina propria (LP). The lymphocytes were counted and phenotypes determined by flow cytometry (αβTCR, γδTCR, CD4, CD8, B cell). IgA levels of small intestinal washings were also examined using ELISA (enzyme‐linked immunoabsorbent assay). Results: IL‐7 dose‐dependently increased total lymphocyte numbers in PPs and the LP. The number of lymphocytes harvested from IE spaces reached a plateau at 1 μg/kg of IL‐7. There were no significant differences in any phenotype percentages at any GALT sites among the groups. IgA levels of intestinal washings were significantly higher in the chow group than in any of the IL‐7 groups, with similar levels in all IL‐7 groups. Conclusions: Exogenous IL‐7 dose‐dependently reverses PN‐induced GALT cell loss, with no major changes in small intestinal IgA levels. IL‐7 treatment during PN appears to have beneficial effects on gut immunity, but other therapeutic methods are needed to restore secretory IgA levels.