Predisposition to Colonic Dysplasia is Unaffected by Continuous Administration of Insulin-like Growth Factor-1 for Twenty Weeks in a Rat Model of Chronic Inflammatory Bowel Disease

Abstract

Background Insulin-like growth factor-I (IGF-I) is currently under evaluation for the treatment of a variety of chronic disease conditions. We investigated the safety of long-term IGF-I administration in a rat model of inflammatory bowel disease which predisposes to the development of dysplasia.

Methods Chronic consumption of dextran sulphate sodium (DSS) by rats manifests a colitis with dysplastic features. Rats consumed 2% DSS for 4 weeks when pumps were implanted to deliver either vehicle or IGF-I for 15 or 20 weeks while rats continued to consume DSS. Features of colitis and dysplasia were assessed at kill.

Results Compared to vehicle, 20 weeks IGF-I significantly increased body weight by 19% and total gut weight by 43%. Colonic crypt depth, proliferative compartment, labelling index, dysplasia, neoplasia and other indices of colitis were not significantly affected.

Conclusions Twenty weeks administration of IGF-I to rats induced growth of the intestine but did not affect the severity of experimentally-induced colitis or the incidence or progression of colonic dysplasia.

Key Words:

• Inflammatory bowel disease
• insulin-like growth factor-I
• dysplasia
• colon cancer
• rat