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: SOD mice were fed n-3-enriched or control diet for 3 weeks before colitis induction by transplantation of CD45RB(high) 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 collalgen 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-1 beta 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.