Predisposition to colonic dysplasia is unaffected by continuous administration of insulin-like growth factor-I for twenty weeks in a rat model of chronic inflammatory bowel disease.
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.
Howarth
G S
GS
Cooperative Research Centre for Tissue Growth and Repair, and Child Health Research Institute, North Adelaide, South Australia, Australia. ghowarth@medicine.adelaide.edu.au
Xian
C J
CJ
Read
L C
LC
D000236:Adenoma / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002432:Cecum / Q000473:pathology; D002908:Chronic Disease; D003110:Colonic Neoplasms / Q000209:etiology* / Q000473:pathology; D016264:Dextran Sulfate / Q000494:pharmacology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D016264:Dextran Sulfate