Technotes

Technotes

Inflammatory Bowel Disease

Introduction



Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory condition of the gastrointestinal tract that is usually manifest as 1 of 2 distinct, but sometimes overlapping clinical entities; ulcerative colitis (UC) and Crohn’s disease (CD). While CD is a multifocal, transmural inflammatory process that can affect any part of the digestive tract, UC is characterized by a superficial, continuous inflammation, which is limited to the large intestine. IBD is most commonly diagnosed between the third and fourth decade of life, with no difference noted between males and females.

Until recently, the clinical treatments for UC and CD were relatively limited, essentially comprising of 5-aminosalicylic acid (ASA) compounds, steroids and azathioprine/ 6-mercaptopurine. In the 1990s, immunoregulatory agents used in IBD were expanded to include methotrexate and cyclosporine in select patient populations. The approval of infliximab (Remicade; Centocor), a chimeric monoclonal antibody directed against tumor-necrosis factor-α (TNFα), for the treatment of CD in 1998 by the FDA launched the era of biologic therapy for IBD.


PharmaLegacy Models and Research Tools


IBD models can be either induced or spontaneously occurring in animals. Induced models include: (i) Animals treated with agents that promote intestinal inflammation, (ii) Rodents that have been genetically manipulated (iii) Immunodeficient animals. As the onset of inflammation is immediate and the procedure is relatively straightforward, chemically induced models of intestinal inflammation have become the most commonly used IBD animal models.  At PharmaLegacy we have validated a complete set of IBD models in rodents.

Model

DNBS induced colitis

DSS induced colitis

 Animal

        SJL/J mice         SHAPE  \* MERGEFORMAT

C57BL/6 mice

 Human disease

Crohn's Disease (CD)

 Ulcerative Colitis (UC)

 Pathogenesis

A Th1-polarized type of T-cell response

 Th1 and Th2 cells play a pathogenic role in the chronic phase

 Clinical 

 symptoms

Weight loss, loose stool/diarrhea, hematochezia (mice), colon shortening

 Pathology  change

Leukocyte infiltration associated with Prominent mucosal and submucosal leukocyte infiltration deep chronic ulceration; Submucosal associated with ulceration; Severe damage of the edema; Inflammation involving the epithelial cell layer and crypts; Submucosal edema; entire length of the bowelInflammation confined to the distal segment of the colon

 1° Endpoints

Colonic weight, colonic length, colonic damage score, body weight change.

 2° Endpoints

Histopathology; Immunohistochemistry; Cytokines/Chemokine Analysis; T cell proliferation;

Infiltration cell types

            DNBS - dinitrobenzene sulfonic acid       DSS - dextran-sulfate sodium    

Related Capabilities




Case Study   -  DNBS Induced IBD in Wistar Rats



Inhibitory effect of sulfasalazine on DNBS induced IBD in Wistar rats
Male Wistar rats (150−160 g) were used in the study. Colitis was induced by intracolonic administration of 0.5 mL DNBS in 30% ethanol. Animals were then treated orally with 300 mg/kg sulfasalazine-1 once daily for 7 days. An equal volume of 30% ethanol was administered as the control. Animals were sacrificed 2 hrs after the last dose.