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

The Prophylactic Use of Bovine Colostrum in a Murine Model of TNBS-Induced Colitis

“…They obtained improvements of DAI and symptoms by using hyperimmune colostrum, on the other hand, the administration of raw BC did not show any significant amelioration on TNBS-induced colitis in mice. Conversely, other authors [8,24] have recently reported that also colostrum from nonimmunized cows can reduced BW losses, DAI and histological score in DSS-induced murine models of IBD. In humans, the administration of BC by enema for 4 weeks improved the clinical and histological score in patients affected by active colitis compared to control [7].…”

“…Currently, the precise mechanisms involved in the pathogenesis of IBD are largely unknown, and a perfect model for their investigation does not exist. For these reasons, in recent years, many animal models and various chemical compounds have been employed to study its pathogenesis [8,26,28]. In our study, we designed the experimental procedures using the haptenic agent TNBS, which induces the disruption of the intestinal barrier and elicits a significant immune response that resembles IBD in regard to clinical symptoms and histopathology [25,26].…”

“…This means that even humans and other animal species can count on BC to achieve health benefits [5,23]. There is emerging evidence that entire or fractioned BC and hyperimmune BC may become promising nutraceuticals that can prevent or alleviate various gastrointestinal disorders including IBD [4,7,8,23,24]. Thus, the present study was undertaken to assess the potential positive impact of a short-term prophylactic oral administration of BC in a murine model of TNBS-induced colitis.…”

“…Finally, BC also contains growth factors that play important roles in the development, maturation, and repair of various tissues including the intestine [3][4][5][6]. Several studies and clinical trials, both in vitro and in vivo on humans and animals, suggest that these beneficial properties of colostrum can be exploited in the prevention and treatment of various gastrointestinal diseases [3,5,7,8].…”

“…In this context, BC has the potential to be considered a natural nutraceutical product that does not show adverse effects and that may be evaluated as an alternative or as a coadjuvant to the synthetic drugs in the prevention and treatment of different gastrointestinal diseases, including IBD [5,8,22]. Nevertheless, studies concerning the clinical use of BC in IBD are still limited, heterogeneous, and controversial; thus, further research is required before recommendations can be made for clinical application [7,23,24].…”