Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis

Background : Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4⁺ cells, increased CD8⁺ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods : Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results : All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points ( P <0.01).
Conclusions : Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.