Biol. Pharm. Bull. 28(11) 2046—2053 (2005)

tion to protect the host by neutralizing infectious agents or injurious substances. This protective mechanism is well balanced and usually does not lead to mucosal damage in the intestine. In a state of disease such as inflammatory bowel disease, various immune responses of the gut-associated lymphoid tissues are exaggerated, resulting in the development of a prolonged and severe inflammation of the intestinal mucosa. Human inflammatory bowel disease is a chronic and idiopathic inflammation of the mucosa of the distal small intestine, the etiology of which is as yet unknown. This inflammatory disease is clinically characterized by two overlapping phenotypes, Crohn’s disease (CD) and ulcerative colitis. CD is a chronic and incurable condition marked by periods of exacerbation and remission. CD is also characterized by transmural inflammation resulting in abdominal pain, diarrhea and weight loss. In addition, recent findings suggest that CD is the result of an excessive Th1 response. Therefore, the use of agents that block the Th1 response or promote a Th2 profile might prove to be beneficial in this disease. However, at this point in time treatment is still mostly symptomatic, aimed at reducing inflammation because neither a specific cause nor factors that determine the degree of disease progression have been identified. Chronic intestinal inflammation induced in mice by intrarectal administration of trinitrobenzene sulfonic acid (TNBS) produces many clinical, histopathologic and immune characteristics that are similar to those of CD in humans. In fact, treatment with TNBS induces chronic colitis characterized by severe transmural inflammation associated with diarrhea, rectal prolapse and weight loss. This inflammation is characterized by a massive infiltration of neutrophils and macrophages, producing high levels of proinflammatory cytokines such as tumor necrosis factor (TNF)a , interleukin (IL)-1b , or IL-6 in early stages of the disease. This is followed by T-cell infiltration, particularly of the CD4 phenotype, resulting in the production of high levels of interferon (IFN)-g and reduced amounts of IL-4. DNA microarray analysis has been applied for the identification of gene transcripts possibly controlling CD. However, it has not been possible to identify a causative gene(s) or gene product that triggers the initial event(s) leading to mucosal inflammation and its progression to CD. It is possible that gene transcripts identified in tissue samples from TNBS-treated mice could represent transcript changes during the initial stage of inflammatory diseases. Upon careful evaluation with those from CD patients, transcripts identified might provide a clue to potential intervention or treatments including gene therapy. The objectives of the present investigation were to identify transcript changes in mucosal samples from TNBS-treated mice and those from CD patients, and to relate these changes for the formulation of transcript changes from the initial and progressive stages to CD development.