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Administration of the hyper-immune bovine colostrum extract IMM-124E ameliorates experimental murine colitis


Spalinger, Marianne R; Atrott, Kirstin; Baebler, Katharina; Schwarzfischer, Marlene; Melhem, Hassan; Peres, Dan R; Lalazar, Gadi; Rogler, Gerhard; Scharl, Michael; Frey-Wagner, Isabelle (2018). Administration of the hyper-immune bovine colostrum extract IMM-124E ameliorates experimental murine colitis. Journal of Crohn's & Colitis:Epub ahead of print.

Abstract

Background/Aims Inflammatory bowel disease (IBD) is accompanied by lesions in the epithelial barrier, which allow translocation of bacterial products from the gut lumen to the host's circulation. IMM-124E is a colostrum-based product, containing high levels of anti-E.coli-LPS IgG and might limit exposure to bacterial endotoxins. Here, we investigated whether IMM-124E can ameliorate intestinal inflammation. Methods Acute colitis was induced in WT C57Bl/6J mice by administration of 2.5% DSS for 7 days. T cell transfer colitis was induced via transfer of 0.5x10 6 naïve T cells into RAG2 -/- C57Bl/6J mice. IMM-124E was administered daily by oral gavage either preventive or therapeutically. Results Treatment with IMM-124E significantly ameliorated colitis in acute DSS colitis and in T cell transfer colitis. Maximum anti-inflammatory effects were detected at an IMM-124E concentration of 100 mg/kg body weight, while 25 mg/kg and 500 mg/kg were less effective. Histology revealed reduced levels of infiltrating immune cells, and less pronounced mucosal damage. Flow cytometry revealed reduced numbers of effector T helper cells in the intestine, while levels of regulatory T cells were enhanced. IMM-124E-treatment reduced the DSS-induced increase of serum levels of LPS-binding protein, indicating reduced systemic LPS exposure. Conclusions Our results demonstrate that oral treatment with IMM-124E significantly reduces intestinal inflammation, via decreasing the accumulation of pathogenic T cells, and concomitantly increasing the induction of regulatory T cells. Our study confirms the therapeutic efficacy of IMM-124E in acute colitis and suggests that administration of IMM-124E might represent a novel therapeutic strategy to induce or maintain remission in chronic colitis.

Abstract

Background/Aims Inflammatory bowel disease (IBD) is accompanied by lesions in the epithelial barrier, which allow translocation of bacterial products from the gut lumen to the host's circulation. IMM-124E is a colostrum-based product, containing high levels of anti-E.coli-LPS IgG and might limit exposure to bacterial endotoxins. Here, we investigated whether IMM-124E can ameliorate intestinal inflammation. Methods Acute colitis was induced in WT C57Bl/6J mice by administration of 2.5% DSS for 7 days. T cell transfer colitis was induced via transfer of 0.5x10 6 naïve T cells into RAG2 -/- C57Bl/6J mice. IMM-124E was administered daily by oral gavage either preventive or therapeutically. Results Treatment with IMM-124E significantly ameliorated colitis in acute DSS colitis and in T cell transfer colitis. Maximum anti-inflammatory effects were detected at an IMM-124E concentration of 100 mg/kg body weight, while 25 mg/kg and 500 mg/kg were less effective. Histology revealed reduced levels of infiltrating immune cells, and less pronounced mucosal damage. Flow cytometry revealed reduced numbers of effector T helper cells in the intestine, while levels of regulatory T cells were enhanced. IMM-124E-treatment reduced the DSS-induced increase of serum levels of LPS-binding protein, indicating reduced systemic LPS exposure. Conclusions Our results demonstrate that oral treatment with IMM-124E significantly reduces intestinal inflammation, via decreasing the accumulation of pathogenic T cells, and concomitantly increasing the induction of regulatory T cells. Our study confirms the therapeutic efficacy of IMM-124E in acute colitis and suggests that administration of IMM-124E might represent a novel therapeutic strategy to induce or maintain remission in chronic colitis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:12 December 2018
Deposited On:24 Jan 2019 09:20
Last Modified:24 Jan 2019 14:34
Publisher:Oxford University Press
ISSN:1873-9946
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Journal of Crohn's & Colitis following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: https://doi.org/10.1093/ecco-jcc/jjy213
OA Status:Closed
Publisher DOI:https://doi.org/10.1093/ecco-jcc/jjy213
PubMed ID:30590526

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Embargo till: 2019-12-13