• 1.

    Collins T. Acute and chronic inflammation. In: Cotran R, Kumar V, Collins T, eds. Robbins pathologic basis of disease. 6th ed. Philadelphia: WB Saunders Co, 1999;7074.

    • Search Google Scholar
    • Export Citation
  • 2.

    Calder PC. Polyunsaturated fatty acids, inflammation, and immunity. Lipids 2001;36:10071024.

  • 3.

    Jarrar D, Chaudry IH, Wang P. Organ dysfunction following hemorrhage and sepsis: mechanisms and therapeutic approaches. Int J Mol Med 1999;4:575583.

    • Search Google Scholar
    • Export Citation
  • 4.

    Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996;87:20952147.

  • 5.

    Calder PC. n-3 polyunsaturated fatty acids and cytokine production in health and disease. Ann Nutr Metab 1997;41:203234.

  • 6.

    Gelin J, Moldawer L, Lonnroth C, et al. Role of endogenous tumor necrosis factor α and interleukin 1 for experimental tumor growth and the development of cancer cachexia. Cancer Res 1991;51:415421.

    • Search Google Scholar
    • Export Citation
  • 7.

    Strassmann G, Kambayashi T. Inhibition of experimental cancer cachexia by anti-cytokine and anti-cytokine-receptor therapy. Cytokines Mol Ther 1995;1:107113.

    • Search Google Scholar
    • Export Citation
  • 8.

    Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001;108:1523.

    • Search Google Scholar
    • Export Citation
  • 9.

    McManus LM, Pinckard RN. PAF, a putative mediator of oral inflammation. Crit Rev Oral Biol Med 2000;11:240258.

  • 10.

    Kroegel C, Virchow JC Jr, Luttmann W, et al. Pulmonary immune cells in health and disease: the eosinophil leucocyte (part I). Eur Respir J 1994;7:519543.

    • Search Google Scholar
    • Export Citation
  • 11.

    Christie PE, Henderson WR Jr. Lipid inflammatory mediators: leukotrienes, prostaglandins, platelet-activating factor. Clin Allergy Immunol 2002;16:233254.

    • Search Google Scholar
    • Export Citation
  • 12.

    Floch A, Bousseau A, Hetier E, et al. RP 55778, a PAF receptor antagonist, prevents and reverses LPS-induced hemoconcentration and TNF release. J Lipid Mediat 1989;1:349360.

    • Search Google Scholar
    • Export Citation
  • 13.

    Poubelle PE, Gingras D, Demers C, et al. Platelet-activating factor (PAF-acether) enhances the concomitant production of tumour necrosis factor-alpha and interleukin-1 by subsets of human monocytes. Immunology 1991;72:181187.

    • Search Google Scholar
    • Export Citation
  • 14.

    LeBlanc CJ, Bauer JE, Hosgood G, et al. Effect of dietary fish oil and vitamin E supplementation on hematologic and serum biochemical analytes and oxidative status in young dogs. Vet Ther 2005;6:325340.

    • Search Google Scholar
    • Export Citation
  • 15.

    LeBlanc CJ, Dietrich MA, Horohov DW, et al. Effects of dietary fish oil and vitamin E supplementation on canine lymphocyte proliferation evaluated using a flow cytometric technique. Vet Immunol Immunopathol 2007;119:180188.

    • Search Google Scholar
    • Export Citation
  • 16.

    Laflamme D. Development and validation of a body scoring system for dogs: a clinical tool. Canine Pract 1997;22(4):1015.

  • 17.

    Mawby DI, Bartges JW, d'Avignon A, et al. Comparison of various methods for estimating body fat in dogs. J Am Anim Hosp Assoc 2004;40:109114.

    • Search Google Scholar
    • Export Citation
  • 18.

    National Research Council, Subcommittee on Dog Nutrition. Nutrient requirements of dogs. Washington, DC: National Academy of Sciences, 1985;23.

    • Search Google Scholar
    • Export Citation
  • 19.

    Association of American Feed Control Officials. 2001 official publication. Oxford, Ind: Association of American Feed Control Officials, 2001.

    • Search Google Scholar
    • Export Citation
  • 20.

    LeMay DR, LeMay LG, Kluger MJ, et al. Plasma profiles of IL6 and TNF with fever-inducing doses of lipopolysaccharide in dogs. Am J Physiol 1990;259:R126R132.

    • Search Google Scholar
    • Export Citation
  • 21.

    Bueno AC, Seahorn TL, Cornick-Seahorn J, et al. Plasma and urine nitric oxide concentrations in horses given below a low dose of endotoxin. Am J Vet Res 1999;60:969976.

    • Search Google Scholar
    • Export Citation
  • 22.

    Yamada K, Asano O, Yoshimura T, et al. Highly sensitive gas chromatographic–mass spectrometric method for the determination of platelet-activating factor in human blood. J Chromatogr 1988;433:243247.

    • Search Google Scholar
    • Export Citation
  • 23.

    Kay-Mugford P, Benn SJ, LaMarre J, et al. In vitro effects of nonsteroidal anti-inflammatory drugs on cyclooxygenase activity in dogs. Am J Vet Res 2000;61:802810.

    • Search Google Scholar
    • Export Citation
  • 24.

    Stewart J. Approximate integration. In: Calculus: early transcendentals. 3rd ed. Pacific Cove, Calif: Brooks/Cole Publishing Co, 1995;459.

    • Search Google Scholar
    • Export Citation
  • 25.

    Kearns RJ, Hayek MG, Turek JJ, et al. Effect of age, breed and dietary omega-6 (n-6): omega-3 (n-3) fatty acid ratio on immune function, eicosanoid production, and lipid peroxidation in young and aged dogs. Vet Immunol Immunopathol 1999;69:165183.

    • Search Google Scholar
    • Export Citation
  • 26.

    Wander RC, Hall JA, Gradin JL, et al. The ratio of dietary (n-6) to (n-3) fatty acids influences immune system function, eicosanoid metabolism, lipid peroxidation and vitamin E status in aged dogs. J Nutr 1997;127:11981205.

    • Search Google Scholar
    • Export Citation
  • 27.

    Vaughn DM, Reinhart GA, Swaim SF, et al. Evaluation of effects of dietary n-6 to n-3 fatty acid ratios on leukotriene B synthesis in dog skin and neutrophils. Vet Dermatol 1994;5:163172.

    • Search Google Scholar
    • Export Citation
  • 28.

    Scott DW, Miller WH Jr, Reinhart GA, et al. Effect of an omega-3/omega-6 fatty acid-containing commercial lamb and rice diet on pruritus in atopic dogs: results of a single-blinded study. Can J Vet Res 1997;61:145153.

    • Search Google Scholar
    • Export Citation
  • 29.

    Scott DW, Buerger RG. Nonsteroidal anti-inflammatory agents in the management of canine pruritus. J Am Anim Hosp Assoc 1988;24:425428.

  • 30.

    Lloyd DH. Essential fatty acids and skin disease. J Small Anim Pract 1989;30:207212.

  • 31.

    Miller W. Fatty acid supplements as anti-inflammatory agents. In: Kirk R, ed. Current veterinary therapy X. Philadelphia: WB Saunders Co, 1989;563565.

    • Search Google Scholar
    • Export Citation
  • 32.

    Freeman LM, Rush JE, Kehayias JJ, et al. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med 1998;12:440448.

    • Search Google Scholar
    • Export Citation
  • 33.

    Abbas A, Lichtman A. Section 4, Chapter 11. In: Abbas A, Lichtman A, eds. Cellular and molecular immunology. 5th ed. Philadelphia: WB Saunders Co, 2003;262.

    • Search Google Scholar
    • Export Citation
  • 34.

    Glauser MP. The inflammatory cytokines. New developments in the pathophysiology and treatment of septic shock. Drugs 1996;52(suppl 2):917.

    • Search Google Scholar
    • Export Citation
  • 35.

    Sadeghi S, Wallace F, Calder P. Dietary lipids modify the cytokine response to bacterial lipopolysaccharide in mice. Immunology 1999;96:404410.

    • Search Google Scholar
    • Export Citation
  • 36.

    Horii T, Satouchi K, Kobayashi Y, et al. Effect of dietary alpha-linolenate on platelet-activating factor production in rat peritoneal polymorphonuclear leukocytes. J Immunol 1991;147:16071613.

    • Search Google Scholar
    • Export Citation
  • 37.

    Oh-hashi K, Takahashi T, Tanabe A, et al. Dietary alpha-lino-lenate suppresses endotoxin-induced platelet-activating factor production in rat kidney. Lipids 1999;34:3137.

    • Search Google Scholar
    • Export Citation
  • 38.

    Akisu M, Huseyinov A, Baka M, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the generation of platelet-activating factor and leukotriene B(4) in hypoxic-ischemic brain in young mice. Prostaglandins Leukot Essent Fatty Acids 2002;67:429433.

    • Search Google Scholar
    • Export Citation
  • 39.

    Mayer K, Merfels M, Muhly-Reinholz M, et al. ω-3 fatty acids suppress monocyte adhesion to human endothelial cells: role of endothelial PAF generation. Am J Physiol Heart Circ Physiol 2002;283:H811H818.

    • Search Google Scholar
    • Export Citation
  • 40.

    Meydani SN, Endres S, Woods MM, et al. Oral (n-3) fatty acid supplementation suppresses cytokine production and lympho-cyte proliferation: comparison between young and older women. J Nutr 1991;121:547555.

    • Search Google Scholar
    • Export Citation
  • 41.

    Meydani SN, Lichtenstein AH, Cornwall S, et al. Immunologic effects of national cholesterol education panel step-2 diets with and without fishderived acid enrichment. J Clin Invest 1993;92:105113.

    • Search Google Scholar
    • Export Citation
  • 42.

    Wallace FA, Miles EA, Calder PC. Activation state alters the effect of dietary fatty acids on proinflammatory mediator production by murine macrophages. Cytokine 2000;12:13741379.

    • Search Google Scholar
    • Export Citation
  • 43.

    Reinhart G. Review of omega-3 fatty acids and dietary influences on tissue concentrations. In: Carey D, Norton S, Bolser S, eds. Recent advances in canine and feline nutritional research: proceedings of the 1996 IAMS international nutrition symposium. Wilmington, Ohio: Orange Frazer Press, 1996;235242.

    • Search Google Scholar
    • Export Citation
  • 44.

    Bauer JE. The potential for dietary polyunsaturated fatty acids in domestic animals. Aust Vet J 1994;71:342345.

Effects of dietary supplementation with fish oil on in vivo production of inflammatory mediators in clinically normal dogs

Casey J. LeBlanc DVM, PhD1, David W. Horohov PhD2, John E. Bauer DVM, PhD3, Giselle Hosgood BVSc, PhD4, and Glenna E. Mauldin DVM, MS5
View More View Less
  • 1 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 2 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 3 Comparative Nutrition Research Laboratory, Department of Small Animal Medicine and Surgery, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77845.
  • | 4 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.
  • | 5 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803.

Abstract

Objective—To evaluate the effect of diets enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on in vivo production of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, prostaglandin E2 (PGE2), and platelet-activating factor (PAF) in dogs.

Animals—15 young healthy dogs.

Procedures—Dogs were randomly allocated to receive an isocaloric ration supplemented with sunflower oil (n = 5), fish oil (5), or fish oil plus vitamin E (5) for 12 weeks. At week 12, in vivo production of inflammatory mediators was evaluated in serum at multiple time points for 6 hours following stimulation with IV administration of lipopolysaccharide (LPS).

Results—Serum activity or concentration (area under the curve) of IL-1, IL-6, and PGE2 significantly increased after LPS injection in all groups but to a lesser extent in dogs receiving the fish oil diet, compared with results for dogs receiving the sunflower oil diet. Serum activity of TNF-α and PAF concentration also increased significantly after LPS injection in all groups but did not differ significantly among groups.

Conclusions and Clinical Relevance—A fish oil–enriched diet consisting of 1.75 g of EPA/kg of diet and 2.2 g of DHA/kg of diet (dry-matter basis) with an n-6:n-3 fatty acid ratio of 3.4:1 was associated with significant reductions in serum PGE2 concentrations and IL-1 and IL-6 activities. Results supported the use of EPA- and DHA-enriched diets as part of antiinflammatory treatments for dogs with chronic inflammatory diseases. Additional studies in affected dogs are warranted to further evaluate beneficial anti-inflammatory effects of EPA- and DHA-enriched diets.

Abstract

Objective—To evaluate the effect of diets enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on in vivo production of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α, prostaglandin E2 (PGE2), and platelet-activating factor (PAF) in dogs.

Animals—15 young healthy dogs.

Procedures—Dogs were randomly allocated to receive an isocaloric ration supplemented with sunflower oil (n = 5), fish oil (5), or fish oil plus vitamin E (5) for 12 weeks. At week 12, in vivo production of inflammatory mediators was evaluated in serum at multiple time points for 6 hours following stimulation with IV administration of lipopolysaccharide (LPS).

Results—Serum activity or concentration (area under the curve) of IL-1, IL-6, and PGE2 significantly increased after LPS injection in all groups but to a lesser extent in dogs receiving the fish oil diet, compared with results for dogs receiving the sunflower oil diet. Serum activity of TNF-α and PAF concentration also increased significantly after LPS injection in all groups but did not differ significantly among groups.

Conclusions and Clinical Relevance—A fish oil–enriched diet consisting of 1.75 g of EPA/kg of diet and 2.2 g of DHA/kg of diet (dry-matter basis) with an n-6:n-3 fatty acid ratio of 3.4:1 was associated with significant reductions in serum PGE2 concentrations and IL-1 and IL-6 activities. Results supported the use of EPA- and DHA-enriched diets as part of antiinflammatory treatments for dogs with chronic inflammatory diseases. Additional studies in affected dogs are warranted to further evaluate beneficial anti-inflammatory effects of EPA- and DHA-enriched diets.

Contributor Notes

Dr. LeBlanc's present address is Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4542.

Dr. Horohov's present address is Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546-0099.

Dr. Mauldin's present address is Western Veterinary Specialist Centre, 1802 10th Ave SW, Calgary, AB T3C 0J8, Canada.

Supported by the Veterinary Clinical Sciences Competative Organized Research Program Fund and Department of Pathobiological Sciences at the Louisiana State University School of Veterinary Medicine.

The authors thank Julie Millard, Gaye Gomilla, and Susan Pourciau for technical assistance.

Address correspondence to Dr. LeBlanc.