Israel Medical Association Journal

The etiology of inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, is uncertain. Studies of specific environmental factors and immune dysfunction have provided limited insight into disease pathogenesis. There is ample evidence that these diseases are in part the result of genetic predisposition. The early search for candidate genes focused on genes involved in the regulation of immune function.

Recent genome wide searches reported several susceptibility loci for Crohn’s disease and ulcerative colitis. The recent identification of the IBD1 gene (NOD2) with mutations that are associated with susceptibility to Crohn’s disease will have a major impact on the understanding of the genetics of this disease.
 

Background: Rectal administration of iodoacetamide induces colitis by blocking sulphhydryl groups and generating inflammatory mediators. Thalidomide, a non-barbiturate hyp­notic, also has an anti-inflammatory effect, presumably by suppressing the production of tumor necrosis factor alpha. In patients with Crohn’s disease, neutralization or suppression of TNFá reduces inflammation.

Objectives: To evaluate the effects of thalidomide in a model of experimental colitis.

Methods: Colitis was induced in rats by intracolonic administration of 3% iodoacetamide. In the treatment group, thalidomide 50 mg/kg was given daily by gavage and continued for 7 days until the rats were sacrificed. Their colons were then processed for wet weight, lesion area, weight of mucosal scraping, myeloperoxidase activity and histology. Serum levels of TNF were determined.

Results: Colonic wet weight, lesion area, myeloperoxidase activity and serum levels of TNFá were significantly lower (P<0.05) in the treatment group (iodoacetamide + thalido­mide) than the control group (iodoacetamide only). Histologi­cally, colonic inflammation in the treated group was markedly decreased.

Conclusions: Thalidomide effectively decreases colitis induced by iodoacetamide. The mechanism is probably associated with inhibition of TNFá, and should be further studied.