Administration of the Hyper-immune Bovine Colostrum Extract IMM-124E Ameliorates Experimental Murine Colitis

• Published in: Journal of Crohn's and colitis Vol. 13; no. 6; pp. 785 - 797
• Main Authors: Spalinger, Marianne R, Atrott, Kirstin, Baebler, Katharina, Schwarzfischer, Marlene, Melhem, Hassan, Peres, Dan R, Lalazar, Gadi, Rogler, Gerhard, Scharl, Michael, Frey-Wagner, Isabelle
• Format: Journal Article
• Language: English
• Published: England 27.05.2019
• Subjects: Animals; Blotting, Western; Cattle; Colitis - drug therapy; Colitis - pathology; Colon - pathology; Colostrum - chemistry; Colostrum - immunology; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Immunoglobulin G - immunology; Immunoglobulin G - therapeutic use; Lipopolysaccharides - immunology; Mice; Mice, Inbred C57BL; Peroxidase - metabolism; novel therapeutic approach in IBD; Systemic LPS exposure
• ISSN: 1873-9946; 1876-4479
• DOI: 10.1093/ecco-jcc/jjy213

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. Acute colitis was induced in WT C57Bl/6J mice by administration of 2.5% dextran sodium sulphate [DSS] for 7 days. T cell transfer colitis was induced via transfer of 0.5 x 106 naïve T cells into RAG2-/- C57Bl/6J mice. IMM-124E was administered daily by oral gavage, either preventively or therapeutically. 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, whereas 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, whereas levels of regulatory T cells were enhanced. IMM-124E treatment reduced the DSS-induced increase of serum levels of lipopolysaccharide [LPS]-binding protein, indicating reduced systemic LPS exposure. 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.