Activation of nuclear factor kappa B in Crohn's disease

Objectives and Design: The location and degree of activation of nuclear fac tor kappa (NF kappa B), a primary transcription factor that plays a regulat ing role in immune and inflammatory responses, was determined in Crohn's di sease using full thickness specimens of bowel collected at surgery. Materials and Methods: Resected specimens of inflamed and non-inflamed bowe l were collected from thirteen patients with Crohn's disease and non-inflam ed bowel from eleven control subjects. Prepared frozen sections were immuno stained using a monoclonal antibody to the activated form of the p65 subuni t of NF kappa B and the number of positive staining cells counted using a L ennox graticule. Results: The number of cells positive for activated NF kappa B was signific antly increased (p = 0.001) in all layers of inflamed Crohn's disease bowel , compared to non-inflamed bowel from controls. There was also a significan t increase (p = 0.009) in the number of positive cells, when compared to no n-inflamed bowel from control subjects, in the submucosa of non-inflamed ar eas of Crohn's disease bowel. Cells positive for activated NF kappa B were provisionally identified by morphological criteria as mostly macrophages wi th some lymphocytes. There was no activation in endothelia. Conclusion: NF kappa B is activated within large mononuclear cells in all l ayers of inflamed areas of the bowel in Crohn's disease and may represent k ey events in the inflammatory process. Increased activation in the submucos a of non-inflamed Crohn's disease bowel provides further evidence of early immunological activation in macroscopically and microscopically uninvolved areas and an underlying abnormal immune system in Crohn's disease.