Dietary &ohgr;-6/&ohgr;-3 Polyunsaturated Fatty Acid Ratios Affect the Homeostasis of Th/Treg Cells in Mice With Dextran Sulfate Sodium–Induced Colitis

Background: This study evaluated the effect of different dietary &ohgr;-6/&ohgr;-3 polyunsaturated fatty acid (PUFA) ratios on modulating helper T (Th) and regulatory T (Treg) lymphocytes in mice with dextran sulfate sodium (DSS)–induced colitis. Methods: There were 3 control and 3 colitis groups. Mice were fed for 24 days with diets with soybean oil (S), a mixture of soybean oil and low fish oil content (LF), or high fish oil content (HF). The ratio of &ohgr;-6/&ohgr;-3 PUFA in the LF diet was 4:1, and that in the HF diet was 2:1. The control groups drank distilled water while colitis groups were provided 2% DSS in drinking water during days 15–19. All mice drank distilled water from days 20–24 for recovery and were sacrificed on day 25. Results: Colitis resulted in higher blood Th1, Th2, and Th17 and lower Treg percentages. Also, plasma haptoglobin and proinflammatory chemokines were elevated in colon lavage fluid. Colitic groups with fish oil had lower inflammatory mediators in the plasma and colon lavage fluid. Furthermore, the percentages of blood Th1, Th2, and Th17 cells were lower, whereas Treg cell percentages were higher than those in the soybean oil group. The colitis group with an &ohgr;-6/&ohgr;-3 PUFA ratio of 2:1 had more pronounced effects than the group with a ratio of 4:1. Conclusions: Diets with an &ohgr;-6/&ohgr;-3 PUFA ratio of 2:1 or 4:1 regulate the Th/Treg balance and attenuate inflammatory mediator production in colitis. Compared with the &ohgr;-6/&ohgr;-3 PUFA ratio of 4:1, the ratio of 2:1 was more effective in reducing inflammatory reactions in DSS-induced colitis.

[1]  Yu-Chen Hou,et al.  A soybean and fish oil mixture with different n-6/n-3 PUFA ratios modulates the inflammatory reaction in mice with dextran sulfate sodium-induced acute colitis. , 2015, Clinical nutrition.

[2]  J. Mayberry,et al.  Is there a role for fish oil in inflammatory bowel disease? , 2014, World journal of clinical cases.

[3]  R. Chapkin,et al.  n3 PUFAs reduce mouse CD4+ T-cell ex vivo polarization into Th17 cells. , 2013, The Journal of nutrition.

[4]  P. Loke,et al.  IL-22-producing CD4+ cells are depleted in actively inflamed colitis tissue , 2013, Mucosal Immunology.

[5]  E. James,et al.  Characterization of CD4+ T cell subsets in allergy. , 2012, Current opinion in immunology.

[6]  P. Calder.  Mechanisms of action of (n-3) fatty acids. , 2012, The Journal of nutrition.

[7]  J. Calixto,et al.  Omega-3 Fatty Acid-Derived Mediators 17(R)-Hydroxy Docosahexaenoic Acid, Aspirin-Triggered Resolvin D1 and Resolvin D2 Prevent Experimental Colitis in Mice , 2011, The Journal of Immunology.

[8]  D. Ganea,et al.  Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis , 2011, Brain, Behavior, and Immunity.

[9]  J. Lupton,et al.  Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice , 2011, British Journal of Nutrition.

[10]  D. Ye,et al.  Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention , 2011, Molecular and Cellular Biochemistry.

[11]  K. Nonomura,et al.  Immunomodulatory effects of eicosapentaenoic acid through induction of regulatory T cells. , 2011, International immunopharmacology.

[12]  R. Flavell,et al.  Recent advances in IL-22 biology. , 2011, International immunology.

[13]  A. Griffiths,et al.  Maintenance of remission in inflammatory bowel disease using omega‐3 fatty acids (fish oil): A systematic review and meta‐analyses , 2011, Inflammatory bowel diseases.

[14]  J. Fenton,et al.  Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in a mouse model of inflammatory colitis. , 2010, Cancer research.

[15]  H. Tajiri,et al.  N‐3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease , 2010, Inflammatory bowel diseases.

[16]  A. Gambero,et al.  Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis , 2010, Lipids in Health and Disease.

[17]  D. Artis,et al.  Pathological versus protective functions of IL-22 in airway inflammation are regulated by IL-17A , 2010, The Journal of experimental medicine.

[18]  R. Luben,et al.  Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study , 2010, European journal of gastroenterology & hepatology.

[19]  Judy H. Cho,et al.  IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease. , 2009, Annual review of medicine.

[20]  P. Alex,et al.  Distinct Cytokine Patterns Identified from Multiplex Profiles of Murine DSS and TNBS‐Induced Colitis , 2009, Inflammatory bowel diseases.

[21]  F. Caprioli,et al.  Th17 immune response in IBD: A new pathogenic mechanism. , 2008, Journal of Crohn's & colitis.

[22]  Y. Wan,et al.  TGF-β and Regulatory T Cell in Immunity and Autoimmunity , 2008, Journal of Clinical Immunology.

[23]  King-Jen Chang,et al.  Effects of omega-3 fatty acids on leukocyte Th1/Th2 cytokine and integrin expression in rats with gut-derived sepsis. , 2007, Nutrition.

[24]  Yu-Chen Hou,et al.  Dietary fish oil enhances adhesion molecule and interleukin-6 expression in mice with polymicrobial sepsis , 2006, British Journal of Nutrition.

[25]  H. Nawata,et al.  An Inverse Correlation of Human Peripheral Blood Regulatory T Cell Frequency with the Disease Activity of Ulcerative Colitis , 2006, Digestive Diseases and Sciences.

[26]  S. O'keefe,et al.  Dietary fatty acids modulate chronic colitis, colitis-associated colon neoplasia and COX-2 expression in IL-10 knockout mice. , 2006, Nutrition.

[27]  R. Chapkin,et al.  Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward the Th2 pole by suppression of Th1 development. , 2005, The Journal of nutrition.

[28]  T. Giese,et al.  Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. , 2005, Gastroenterology.

[29]  Agneta Karlsson,et al.  Acute colitis induced by dextran sulfate sodium progresses to chronicity in C57BL/6 but not in BALB/c mice: correlation between symptoms and inflammation. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[30]  J. Glickman,et al.  Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Boehmer,et al.  Mechanisms of suppression by suppressor T cells , 2005, Nature Immunology.

[32]  A. Simopoulos,et al.  The importance of the ratio of omega-6/omega-3 essential fatty acids. , 2002, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[33]  E. Bloemena,et al.  Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines , 1998, Clinical and experimental immunology.

[34]  G. Holmes,et al.  Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. , 1992, Gut.

[35]  G. Triadafilopoulos,et al.  Fish oil fatty acid supplementation in active ulcerative colitis: a double-blind, placebo-controlled, crossover study. , 1992, The American journal of gastroenterology.

[36]  J. Barton,et al.  Gut lavage fluid proteins as markers of activity of inflammatory bowel disease. , 1991, Scandinavian journal of gastroenterology.

[37]  R. Alaniz,et al.  Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) PUFA in Fat-1 mice. , 2012, The Journal of nutrition.

[38]  M. Boirivant,et al.  Inflammatory bowel disease. , 2012, Oral diseases.