|Sonea, I - IOWA STATE UNIV., AMES|
|Wannemuehler, M - IOWA STATE UNIV., AMES|
Submitted to: Canadian Symposium on Neuroimmune Biology
Publication Type: Abstract Only
Publication Acceptance Date: June 10, 2000
Publication Date: N/A
Technical Abstract: T-cell receptor-alpha deficient (TCRalpha-) mice spontaneously develop chronic inflammatory bowel disease (IBD); however, the onset of the disease is very variable. By infecting TCRalpha- mice at 1 wk of age with Cryptosporidium parvum, the onset of IBD-like lesions is hastened; by 3 wk postinfection, early IBD-like lesions are present uniformly in over 98% of infected TCRalpha- mice. Using autoradiography, we found that substance P binding sites were dramatically upregulated in the gut of TCRalpha- mice with IBD, and that most of these sites corresponded to neurokinin-1 receptors. We, therefore, sought to determine whether administration of a specific neurokinin-1 receptor antagonist (NK1R-A) would prevent or moderate the development of IBD-like lesions in this model. At 1 wk of age, TCRalpha- mice were given vehicle or NK1R-A orally, and infected with C. parvum 2 h later. Mice were treated daily until euthanasia 3 wk postinfection. Histologically, 6/7 control TCRalpha- mice had evidence of IBD-like lesions, whereas TCRalpha- mice treated with the NK1R-A had no IBD-like lesions (8/8). We concluded that the neurokinin-1 receptor was important in the induction of IBD-like lesions in this model. Studies are underway to determine whether administration of the NK1R-A can moderate the severity of established IBD-like lesions in this model, and whether specific types or subsets of immune cells express or upregulate the expression of the neurokinin-1 receptor in this murine model of inflammatory bowel disease.