Efficacy of a Transforming Growth Factor β2 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 β2 (TGF-β2), 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-β2 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-β2 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-β2 or a control enteral diet (Diet-B) not rich in TGF-β2. 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-α 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-β2 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-β2 containing enteral diets as one mode of therapy for Crohn’s disease.

• IBD
• Crohn’s disease
• TGF-β2
• enterocolitis

Modulen™ was provided by Nestle’ USA. Dr. DM Rennick provided the IL-10 deficient mouse-breeding colony. We appreciate the nutritional input from Laura Czerkies, consulting dietitian.

Notes

This research was supported by the National Institutes of Health grants AA01762, AA10496, Jewish Hospital Foundation and the Department of Veterans Affairs and an unrestricted educational gift from Nestle’ USA.

Presented in part at the Annual Meeting of American College of Nutrition, San Antonio, Texas, October 2002.