Inflammatory Bowel Disease (IBD) is a group of inflammatory conditions of the colon and small intestine.  The major types are Ulcerative Colitis (UC) and Crohn’s Disease (CD). Human IBD is a chronic relapsing/remitting inflammatory condition of unknown origin that affects an estimated 3-4 million patients in Europe and the U.S.

The disease is characterized by infiltration of inflammatory cells into the mucosa of the digestive tract. UC and CD are distinguished by location and nature of the inflammation.

CD: discontinuous inflammation in any part of the digestive system (primarily the ileum of the Small Intestine and/or the colon) that extends deeply into the layers of the intestine wall. Most commonly CD affects the last part of the Small Intestine (terminal ileum) and parts of the large intestine. (CD is also referred to as granulomatous enteritis, enteritis or colitis).

UC: continuous superficial mucosal inflammation almost exclusively restricted to the colon.

Animal models have proven to be useful in displaying conditions of intestinal inflammation in the Small Intestine and colon for both CD and UC that resemble important immunological and histopathological aspects of human IBD.

The following rodent models of IBD are available at Washington Biotechnology:

 

TNBS-Induced IBD

A single intrarectal administration of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) in Sprague-Dawley rats provides an acute model for human Inflammatory Bowel Disease. This model is widely used, reliable, rapid (1 week) and cost-effective.  

 

DSS-Induced IBD: Acute and Chronic

 

DSS polymers in drinking water induce acute or chronic colitis due to toxicity effects on gut epithelial cells and on the integrity of the mucosal barrier.

 

Acute:

 

Disease induction is via 4% Dextran Sodium Sulfate (DSS) in drinking water of study animals (C57BL/6 male mice) for 5 days.

 

          Chronic:

Disease induction through 3 cycles of 2% DSS (7 days)/regular water (7 days) for C57BL/6 male mice. Dosing can be initiated at any time during the study to determine either prophylactic or therapeutic efficacy.

 

Indomethacin-Induced Inflammation of the Small Intestine

 

Indomethacin induces inflammation of the small-intestinal mucosa leading to ulceration. In rats indomethacin-induced lesions occur in the jejunum and ileum. Subcutaneous injection of indomethacin produces acute injury and inflammation of the distal jejunum and proximal ileum. Epithelial injury, as measured by mucosal permeability, is significantly elevated one day after indomethacin injection. This valuable model resembles human Crohn’s Disease in location (small intestine) and severe nature of the inflammatory injury.

 

 

 

Overview of Washington Biotechnology IBD Models

 

 

TNBS-Induced Acute IBD:                  

Species:                                 Rat (Sprague-Dawley) or Mouse (Balb/c)

Study Duration:                      1 week

Readouts:                              Daily observations and body weights

Terminal colonic tissue scores: adhesions, strictures, ulcers, wall thickness

                                             Colon length and weight

Histopathology on colon tissue: inflammation, edema, gland loss, neutrophil infiltration

 

DSS-Induced IBD – Acute:

Species:                                 C57BL/6 Mouse (male)

Study duration:                      2 weeks

Readouts:                              Disease sign scores (every other day): stool consistency, anal prolapse. Fecal blood

                                                            Body weights daily

                                                            Colon length and weight

Optional: Histopathology on colon tissue for scores of inflammation, edema, gland loss, erosion  and neutrophil infiltration.     

 

DSS-Induced IBD – Chronic:

Species:                                 C57BL/6 Mouse (male)

Study Duration:                      5 weeks

Readouts:                              Disease scores every other day: stool consistency, anal prolapse, fecal blood.

                                             Body weights daily.

                                             Colon length and weight.

Optional: Histology on colon tissue for scores of inflammation, edema, gland loss, erosion and neutrophil infiltration.

 

Indomethacin-Induced IBD (Small Intestine):

Species:                                 Rat (Wistar)

Study Duration:                      1 week

Readouts:                              Disease sign scores at termination: adhesions, transmural ulceration and inflammation.

                                             Length of ulcerated area.

                                             Length of inflamed area.

Small intestine (or sections: ileum, duodenum, jejunum) is collected for optional histopathology.

 

          The WBI Models for IBD may be run as prophylactic or therapeutic studies. Positive controls include sulfasalazine, prednisolone and Enbrel (etanercept).

A Custom Protocol is designed for a study to meet Sponsor’s requirements for dosing regimen and choice of deliverables.

          Deliverables:

·        Blood (serum or plasma)

·        Disease scores, organ length and weight (colon or small intestine depending on model)

·        Final Report includes all materials, procedures, clinical scores of disease severity, body weights and statistical analysis of readouts.

·        Histopathology scoring of collected tissue (colon or small intestine), blocks and slides and photomicrographs.

 

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