Small Intestinal Inflammation Models

In Vivo Models for Small Intestinal
Inflammation Research

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Drug discovery for acute enteritis is challenging due to its varied causes, from infections to autoimmune and inflammatory triggers. Targeted drugs and novel therapeutics are essential for symptom relief and preventing complications, especially given the rise in antimicrobial resistance. In vivo models of acute small intestinal inflammation are crucial for understanding disease mechanisms and testing treatments. These models allow researchers to develop more effective therapies and evaluate in vivo efficacy. Utilize our validated in vivo models and in vivo and in vitro pharmacology services for comprehensive preclinical research testing to strengthen your drug discovery program and improve treatment outcomes.

POLY I:C-INDUCED SMALL INTESTINAL INFLAMMATION MODEL

Model Summary

The poly I:C-induced small intestinal inflammation model in C57BL/6 mice, a model of acute enteritis, is induced by administering polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of retroviral genomic double-stranded RNA. Poly I:C activates pattern recognition receptors, triggering pro-inflammatory cytokine release, immune cell recruitment, and mucosal damage marked by epithelial injury and barrier loss. This results in severe small intestinal injury, marked by intestinal wall thinning, mucosal erosion, villous blunting, elevated serum IL-15, and upregulation of transglutaminase 2. These cytokine and histopathological changes model aspects of human Celiac disease and rotavirus infection providing valuable insights for disease pharmacology studies.

Validation Data

Changes in body weight from study day 6 for normal controls (orange bar; n=3) and poly I:C-induced small intestinal inflammation models (red bar; n=5).

Duodenums collected at necropsy from normal controls (orange bar; n=3) and poly I:C-induced small intestinal inflammation models (red bar; n=5) were scored on a scale of 0-5 for severity of inflammation, with 0 = no inflammation and 5 = severe inflammation. *p<0.05 Mann-Whitney U test vs poly I:C model.

Section of small intestine (duodenum) from a poly I:C-induced small intestinal inflammation model stained with hematoxylin & eosin (H&E). E identifies edema.

ANTI-CD3-INDUCED SMALL INTESTINAL INFLAMMATION MODEL

Model Summary

The anti-CD3-induced small intestinal inflammation model in Balb/c mice is used to study immune-mediated intestinal inflammation. In this model, anti-CD3 antibodies target CD3 receptors on T cells, activating them and triggering inflammatory responses in the small intestine. This activation leads to mucosal injury, characterized by epithelial cell damage, immune cell infiltration, and disruption of barrier function.

Validation Data

Anti-CDS-Induced Small Intestinal Inflammation Model Validation Data

Changes in body weight from study day 6 for normal controls (orange bar; n=3) and anti-CD3-induced small intestinal inflammation models (red bar; n=5). *p<0.05 student’s t-test comparison to anti-CD3 model.

Anti-CDS-Induced Small Intestinal Inflammation Model Validation Data 2 Small intestines collected at necropsy from normal controls (n=3) and anti-CD3-induced small intestinal inflammation models (n=5) were scored on a scale of 0-5 for inflammation, gland loss, and erosion. Summed scores of the key disease features in the duodenum (red bars), jejunum (grey bars), ileum (white bars) and total small intestine (orange bars) were compared between the two groups. *p<0.05 student’s t-test comparison to anti-CD3 model.

Anti-CDS-Induced Small Intestinal Inflammation Model Validation Data 3

Section of small intestine (ileum) from an anti-CD3-induced small intestinal inflammation model stained with H&E. M identifies gland loss.

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Histopathological Assessment

Histopathology is essential in developing therapies for acute small intestinal inflammation, offering insights into the extent of inflammation, tissue damage, and cellular infiltration. This analysis helps identify pathological mechanisms driving the disease and asses in vivo efficacy of therapies. Intestinal sections are stained and microscopically examined by a board-certified veterinary pathologist for key disease features, including inflammation, gland loss, erosion, hyperplasia, and mucosal lymphoid aggregates. Learn more about our histological capabilities.

Additional Endpoints

We realize that demonstrating the in vivo efficacy of novel therapeutics may require assessing endpoints. As a full-service CRO, we offer a comprehensive range of in vivo and in vitro pharmacology services to provide you with the precise data needed to assess your therapeutic. Simply choose your desired endpoints or consult with our team of experts to customize the project to meet your preclinical research needs.