Dietary n-3 polyunsaturated fatty acids reduce disease and colonic proinflammatory cytokines in a mouse model of colitis.
BACKGROUND
n-3 polyunsaturated fatty acids (PUFAs) reduce the severity of chronic inflammatory bowel disease, probably by means of reduction of immune cell activation or enhancement of the epithelial barrier. Using the severe combined immunodeficient (SCID) mouse model of colitis, this study examined the effect of dietary n-3 PUFAs on development of colitis and on immunologic, epithelial, and matrix parameters in the intestines of control and colitic animals.


METHODS
SCID mice were fed n-3-enriched or control diet for 3 weeks before colitis induction by transplantation of CD45RB T cells and maintained on the same diet for 4 to 8 weeks. Phenotype of infiltrating cells, epithelial ZO-1 protein, and mucosal type I collagen were assessed by immunohistology and tissue cytokines by ELISA.


RESULTS
Transplanted n-3-fed animals had significantly reduced pathology scores, colonic tumor necrosis factor-alpha, interleukin-12, and interleukin-1beta compared with animals fed standard diet. Proinflammatory cytokines were reduced despite a similar level of immune cell infiltration by T cells, CD11c cells, and CD11b cells. Neutrophil infiltration was significantly reduced in n-3-fed control and colitic mice, and other myeloid populations were reduced in mice on the n-3 diet. Epithelial ZO-1 expression was increased, and myofibroblast activation significantly decreased in transplanted n-3-fed animals compared with standard diet mice. Submucosal collagen synthesis was enhanced in n-3-fed mice.


CONCLUSIONS
Dietary n-3 PUFAs reduced clinical colitis and colonic immunopathology in this model of colonic inflammation by decreasing proinflammatory cytokine synthesis, reducing myeloid cell recruitment and activation, and enhancing epithelial barrier function and mucosal wound healing mechanisms.
Whiting
Christine V
CV
Veterinary Pathology Infection and Immunity, School Clinical Veterinary Sciences, University of Bristol, Bristol, United Kingdom. C.V.Whiting@bristol.ac.uk
Bland
Paul W
PW
Tarlton
John F
JF
D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D007378:Interleukins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha