Safety and efficacy of the immunosuppressive agent 6-tioguanine in murine model of acute and chronic colitis
Abstract
Oral thiopurines are effective and widely used in treatment of inflammatory bowel disease (IBD) in humans, although their use is limited due the development of adverse events. Here, we examine the efficacy and toxicity of oral treatment with 6-tioguanine (6-TG) and azathioprine (AZA) in a murine model of IBD.
In chronic colitis, all thiopurine derivatives improved colitis, 20 mu g of 6-TG per dose was superior. High doses of 6-TG led to significant weight loss at the end of the therapy, but none of the thiopurine derivatives increased levels of serum ALT.
Both thiopurine derivatives reduced the proportion of apoptotic T helper cells, but a high production of both IL-6 and TGF-beta was observed only in colon of AZA-treated mice. Use of 6-TG in the treatment of experimental colitis in mice appears superior to AZA