Longitudinal evaluation of DSS-induced murine ulcerative colitis in vivo

Abstract

Background: Ulcerative Colitis is a chronic inflammatory disease affecting the rectum to the proximal end of the colon. Today, no cure for the disease exists, only limited treatment options meant to induce remission. However, Ulcerative colitis remains a big public health concern with disease management costs in Europe ranging between 12 - 29 billion euros per year as per the latest estimates. Hence, it is prudent that lasting medical interventions are found, due to increasing pressure on public health resources as prevalence of ulcerative colitis continues to rise. We sought to establish a dextran sodium sulfate induced disease model for evaluation of novel therapies that were on the pipeline, as well as revolutionize diagnostic strategies to be more inflammation specific as compared to what exists in the clinics today.

Methods: 2% w/v of Dextran Sodium Sulfate was used to induce acute murine colitis in wild type C57BL/6NCrl mice. Body weight loss, compilation of disease activity index (DAI), Colonoscopy, Colon wall thickness as measured by magnetic resonance imaging (MRI), ex vivo histology was used to evaluate the onset and longitudinal development of murine ulcerative colitis. A novel biomarker for the evaluation active murine colon inflammation by the tracking of Ly6G neutrophils using PET/CT was also evaluated.

Results: Significant loss of body weight and an elevated DAI were recorded starting at day 6 in the 2% DSS group in comparison to the controls. Colitis score as evaluated using colonoscopy significantly elevated starting day 6, 13 and finally 21. Colon wall thickness as measured by MRI was also elevated starting day 6, 13 and finally 21. Ly6G neutrophils as evaluated by PET/CT were significantly recruited to inflamed colons of the 2% DSS placebo in comparison to both controls and 2% DSS depleted group, 24 and 48 hrs after initial administration on day 6 of 64Cu Ly6G NODAGA radiotracer, however in the subsequent timepoints no Ly6G accumulation was observed.

Conclusion: DSS induced colitis is an inexpensive, easy to establish disease model for the interrogation of the proposed etiologies of ulcerative colitis with obvious differences between control and DSS mice using colonoscopy, increase in colon wall thickness and ex vivo histology. Ly6G neutrophil cell tracking show promise as a novel biomarker for the longitudinal characterization of active murine colitis in vivo, hence facilitating delineation of active and quiescent states of the disease; important indexes especially during drug discovery.