Efficacy of a transforming growth factor beta 2 containing nutritional support formula in a murine model of inflammatory bowel disease.
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.
Oz
Helieh S
HS
Department of Medicine, Section of Gastroenterology/Nutrition, Rush University Medical Center, Chicago, Illinois 60612, USA. helieh_oz@rush.edu
Ray
Mukunda
M
Chen
Theresa S
TS
McClain
Craig J
CJ
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001053:Apolipoproteins / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000178:diet therapy*; D018664:Interleukin-12 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018529:Nutritional Support / Q000379:methods*; D000685:Serum Amyloid A Protein / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D053781:Transforming Growth Factor beta2; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D001053:Apolipoproteins; D016207:Cytokines; D007166:Immunosuppressive Agents; D020382:Interleukin-18; D000685:Serum Amyloid A Protein; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12