Enhanced survival and mucosal repair after dextran sodium sulfate–induced colitis in transgenic mice that overexpress growth hormone☆☆☆

Abstract 

Background & Aims: Growth hormone (GH) is used as therapy for inflammatory bowel disease (IBD), but the specific effects on intestine are unknown. Transgenic mice overexpressing GH (MT1-bGH-TG) were used to test whether increased plasma GH levels alter inflammation or crypt damage during dextran sodium sulfate (DSS)-induced colitis. Methods: MT1-bGH-TG and wild-type (WT) littermates were given 3% DSS for 5 days followed by up to 10 days of recovery. Colitis and epithelial cell proliferation were evaluated histologically. Plasma insulin-like growth factor (IGF)-I and colonic IGF-I, interleukin (IL)-1β, and intestinal trefoil factor (ITF) messenger RNAs (mRNAs) were measured. Results: DSS induced similar disease onset in MT1-bGH-TG and WT. More MT1-bGH-TG survived than WT. By recovery day 7, MT1-bGH-TG had less inflammation and crypt damage, elevated plasma IGF-I, and increased colonic ITF expression relative to WT. Colonic IL-1β was elevated in DSS-treated MT1-bGH-TG and WT, but IL-1β mRNA abundance correlated with disease only in WT. MT1-bGH-TG showed earlier increases in epithelial cell proliferation than WT during recovery but only WT showed atypical repair. Conclusions: GH does not alter susceptibility to acute DSS-induced colitis but enhances survival, remission of inflammation, and mucosal repair during recovery. GH therapy may be beneficial during active IBD by improving mucosal repair.

GASTROENTEROLOGY 2001;120:925-937

Abbreviations:  BrdU , 5'-bromodeoxyuridine, DSS , dextran sodium sulfate, EGF , epidermal growth factor, IGF , insulin-like growth factor, ITF , intestinal trefoil factor, rhGH , recombinant human growth factor, SBS , short bowel syndrome, TGF , transforming growth factor, WT , wild-type