Model Description

In the TNBS colitis model, disease is induced by administration of an enema containing TNBS and ethanol. Ethanol is given to induce breaks of the mucosal barrier that will allow TNBS to enter and chemically modify colonic proteins rendering them immunogenic to the host immune system. The colonic inflammation developed, resembles much to Crohn’s disease pathology resembling Crohn's Disease in the distribution and location of lesions as well as to the Th1 mediated inflammatory response. 

Preclinical Efficacy Evaluation

Study design

A Tg197/TNBS study is normally completed  in 2 weeks time. It involves a presensitization step performed on day -7 followed by TNBS induction on day 0.  A standard protocol involves a prophylactic regimen with administration of therapeutics starting at day -1 before TNBS induction.

Read-out parameters

  • body weight and body temperature measured and recorded daily
  •  lethality
  •  histopathological evaluation of mouse colon sections
  •  ex vivo colon tissue culture and local cytokine levels measurement
Body weight change and histopathological evaluation are two of the most important evaluation tools of the Tg197TNBS model. Therapeutic regimen with Humira significantly improves all signs of pathology. 
                                                        
Ex vivo colon tissue culture from TNBS colitis in Tg197 mice.  Human TNF levels are significantly elevated in this model while treatment with Humira leads to a spectacular reduction.

Bibliography

1. Neurath MF, Fuss I, Pasparakis M, Alexopoulou L, Haralambous S, Meyer zum Büschenfelde KH, Strober W, Kollias G. 1997, "Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice"  Eur. J. Immunol., 27, 1743-50. (view article).
This paper provides direct evidence for the role of TNF in chronic intestinal inflammation using TNBS colitis in Tg197 mice as a model and encourages further clinical trials with anti-TNF therapeutics for the treatment of Crohn's disease.