Efficacy of a transforming growth factor beta 2 containing nutritional support formula in a murine model of inflammatory bowel disease

Abstract

Objective: Dietary, environmental and genetic events may influence host susceptibility to inflammatory bowel diseases (IBD). Transforming growth factor beta 2 (TGF-beta 2), a multifunctional polypeptide (cytokine) present in human and bovine milk, plays a critical role in the development of tolerance, the prevention of autoimmunity, and in anti-inflammatory responses. TGF-beta 2 is a potent inhibitor of intestinal epithelial cell (IEC) growth and stimulates IEC differentiation. The objective of this study was to determine whether a diet containing TGF-beta 2 modulates intestinal injury and immune responses in an Interleukin-10 knockout (IL-10-/-) mouse model of IBD.

Methods: Five-week-old IL-10-/- mice (in BALB/c background) reared in our transgenic facility were fed either an enteral diet (Diet-A) containing TGF-beta 2 or a control enteral diet (Diet-B) not rich in TGF-beta 2. Mice were weighed weekly, monitored for illness and euthanized after eight weeks on the diet.

Results: Final weights were 28 +/- 1.2 g (58.2% gain) for Diet-A mice and 23 +/- 1.6 g (32.9% gain) for Diet-B mice (p = 0.0194). The hematocrits were 48.3% for Diet-A compared to 42% for Diet-B mice (p = 0.0021). Mice on Diet-A had significantly lower serum TNF-alpha concentrations. Forty-four percent of mice on Diet-B developed severe diarrhea and rectal prolapse compared with none on Diet-A. Evaluation of intestinal pathology (score 0-4) revealed that animals fed Diet-A had a score of 2.1 +/- 0.4 compared to 3.2 +/- 0.36 in the Diet-B group (p = 0.040). The acute phase protein, serum amyloid A (SAA), was 3.8 times higher in the Diet-B group (p = 0.0038).

Conclusions: IL-10-/- mice fed a TGF-beta 2 containing diet gained more weight, did not develop diarrhea or prolapse, had lower pathological scores, and lower SAAs. These data further support the use of TGF-beta 2 containing enteral diets as one mode of therapy for Crohn's disease.