Anti-CD40 Colitis in Mice
Induction of Anti-CD40 Colitis in Mice:
On study day 0, female C57BL/6 Rag2-/-(n12) or CB-17 SCID mice are injected (IP) with anti-CD40 IgGa monoclonal antibodies (mAb) to induce innate ulcerative colitis.
Injection of an agonistic CD40 monoclonal antibody (mAb) to T and B cell-deficient mice has been shown to be sufficient to induce a pathogenic systemic and intestinal innate inflammatory response with intestinal inflammation associated with interleukin-23 (IL-23)(p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine1.
- Begin dosing on study day 0 and continue until necropsy on day 7.
- Route of administration: SC, PO, IP, IV, IC
From each animal, the entire colon is harvested, inspected visually, measured for length, and weighed.
The colon is cut into Proximal and Distal halves and collected for processing and embedding. Each half is sectioned into 3 equidistant pieces and these sections are stained to quantitate inflammation, gland loss and epithelial loss (hematoxylin & eosin), which are scored according to these methods.
Sample Data (Click on Image to Enlarge):
Representative Photomicrographs of Colons
For additional examples of positive controls, please contact us.
The CD40-CD154 pathway is important in the pathogenesis of inflammatory bowel disease (IBD), a gastrointestinal disorder that can manifest as Crohn’s disease (CD) or ulcerative colitis (UC). Injection of an agonistic CD40 monoclonal antibody (mAb) to T and B cell-deficient mice has been shown to be sufficient to induce a pathogenic systemic and intestinal innate inflammatory response with intestinal inflammation associated with interleukin-23 (IL-23)(p19) mRNA-producing intestinal dendritic cells and IL-17A mRNA within the intestine1. IL-23(p19)- or IL-23R-deficient mice are resistant to IBD, and the inhibition of IL-23 by anti-p19 neutralizing mAbs blocks organ-specific autoimmune inflammation. IL-23(p19), IL-12(p40), and IL-17A expression is elevated in human inflamed gut from CD and ulcerative colitis patients, and experimental and clinical data have pointed to IL-23 as a therapeutic target for the treatment of IBD2.
- Blood collection
- Feces collection
- Disease Activity Index (DAI)
- PK/PD blood collections
- Cytokine/chemokine analysis via Luminex(R)
- Other sandwich ELISAs
- CBC/clinical chemistry analysis
- Soft tissue collection
- Histopathologic analysis
- Immunohistochemistry analysis
- Uhlig HH, McKenzie BS, Hue S, et al. Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity. 2006;25:309–318. doi: 10.1016/j.immuni.2006.05.017
- Cayatte C, Joyce-Shaikh B, Vega F, et al. Biomarkers of therapeutic response in the IL-23 pathway in inflammatory bowel disease. Clin Transl Gastroenterol. 2012; 3(e10). doi: 10.1038/ctg.2012.2