Results - IMM-124E Ameliorates Colits

P0894 - ADMINISTRATION OF IMM-124E AMELIORATES COLITIS

Spalinger M.R.¹, Atrott K.¹, Bäbler K.¹, Melhem H.¹, Peres D.R.², Lalazar G.³, Rogler G.¹, Scharl M.¹, Frey-Wagner I.^{1 1}University Hospital Zurich, Department of Gastroenterology and Hepatology, Zurich, Switzerland, ²Immuron Limited, Melbourne, Australia, ³The Rockefeller University, Laboratory of Cellular Biophysics, New York, United States

Introduction: 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. Systemic exposure to certain bacterial products, including lipopolysaccharide (LPS) elicits strong immune responses, and thereby contributes to the pathogenesis and perpetuation of IBD. LPS exposure in particular, promotes production of pro-inflammatory cytokines, and affects immune cell activation. Colostrum contains high levels of immunglobulins (Ig), which neutralize bacteria-derived antigens in the intestine, and thereby prevent systemic translocation of bacterial products. IMM-124E is a colostrum-based product, containing high levels of anti-LPS IgG, and therefore prevents systemic exposure to LPS. Since LPS is involved in IBD pathogenesis, we here investigated whether IMM-124E can ameliorate symptoms of intestinal inflammation.

Aims and Methods: Acute colitis was induced in WT C57B6 mice by administration of 2% DSS in the drinking water for 7 days. T cell transfer colitis was induced via transfer of 0.25x10^6 naïve T cells into RAG2^-/- C57B6 mice. IMM-124E was administered daily by oral gavages throughout the experiment (acute DSS colitis) or upon onset of colitis symptoms, namely weight loss and macroscopically inflamed colon as visible by colonoscopy (T cell transfer colitis).

Results: In acute DSS-induced colitis, treatment with IMM-124E significantly ameliorated colitis, as observed by reduced weight loss (p< 0.01), lower endoscopic colitis score (MEICS score; p< 0.05), decreased myeloperoxidase levels (p< 0.01), and reduced shortening of the colon (p< 0.05). Histology of the terminal and proximal colon confirmed reduced colitis (p< 0.05). In the T cell transfer colitis model, therapeutic IMM-124E administration had similar effects and resulted in significant alleviation of colitis symptoms, including reduced disease activity scores and reduced levels of macroscopically detectable colitis in mouse endoscopy (p< 0.05 for both). Maximum anti-inflammatory effects were detected by an IMM-124E concentration of 100 mg/kg body weight. At 25 and 500 mg/kg IMM-124E, the anti-inflammatory effects were also detectable, but clearly less pronounced. Further, histology revealed reduced levels of infiltrating immune cells, and less pronounced mucosal damage (p< 0.05). In line with these findings, levels of IFN-g+ T cells and IL-17+ T cells were clearly reduced in mesenteric lymph nodes (p< 0.01) and the lamina propria (p< 0.05), while levels of FoxP3+ regulatory T cells were enhanced (p< 0.01) in mice treated with IMM-124E, when compared to control mice that received BSA.

Conclusion: Our results demonstrate that treatment with IMM-124E significantly reduces intestinal inflammation via reducing the accumulation and differentiation of pathogenic T cells, while concomitantly enhancing the induction of regulatory cells. This may suggest that inhibiting LPS-mediated effects on the mucosal immune system ameliorates colitis. Summarized, our findings indicate that IMM-124E administration might represent a novel therapeutic strategy to induce or maintain remission in IBD patients.

Disclosure: Nothing to disclose