Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2003;38(4):343–352. doi: 10.1007/s11745-003-1068-y

n−3 Polyunsaturated fatty acids and inflammation: From molecular biology to the clinic

Philip C Calder 1,✉
PMCID: PMC7101988  PMID: 12848278

Abstract

The immune system is involved in host defense against infectious agents, tumor cells, and environmental insults. Inflammation is an important component of the early immunologic response. Inappropriate or dysfunctional immune responses underlie acute and chronic inflammatory diseases. The n−6 PUFA arachidonic acid (AA) is the precursor of prostaglandins, leukotrienes, and related compounds that have important roles in inflammation and in the regulation of immunity. Feeding fish oil results in partial replacement of AA in cell membranes by EPA. This leads to decreased production of AA-derived mediators, through several mechanisms, including decreased availability of AA, competition for cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, and decreased expression of COX-2 and 5-LOX. This alone is a potentially beneficial anti-inflammatory effect of n−3 FA. However, n−3 FA have a number of other effects that might occur down-stream of altered eicosanoid production or might be independent of this effect. For example, dietary fish oil results in suppressed production of proinflammatory cytokines and can modulate adhesion molecule expression. These effects occur at the level of altered gene expression. Fish oil feeding has been shown to ameliorate the symptoms of some animal models of autoimmune disease and to protect against the effects of endotoxin. Clinical studies have reported that oral fish oil supplementation has beneficial effects in rheumatoid arthritis and among some asthmatics, supporting the idea that the n−3 FA in fish oil are anti-inflammatory. There are indications that the inclusion of fish oil in enteral and parenteral formulae is beneficial to patients.

Keywords: Rheumatoid Arthritis, Arachidonic Acid, Polyunsaturated Fatty Acid, Eicosanoid, Atopic Disease

Abbreviations used

AA

arachidonic acid

COX

cyclooxygenase

FLAP

5-lipoxygenase activating protein

GM-CSF

granulocyte macrophage colony stimulating factor

HETE

hydroxyeicosatetraenoic acid

HPETE

hydroperoxyeicosatetraenoic acid

ICAM-1

intercellular adhesion molecule-1

IFN

interferon

IκB

inhibitory subunit of NFκB

IκK

IκB kinase

IL

interleukin

LOX

lipoxygenase

LPS

lipopolysaccharide

LI

leukotriene

MMP

matrix metalloproteinase

NFκB

nuclear factor κB

PG

prostaglandin

PPAR

peroxisome proliferator-activated receptor

SIRS

systemic inflammatory response syndrome

TIMP

tissue inhibitor of metalloproteinase

TNF

tumor necrosis factor

TX

thromboxane

VCAM-1

vascular cell adhesion molecule-1

References

  • 1.Calder P.C. Polyunsaturated Fatty Acids, Inflammation and Immunity. Lipids. 2001;36:1007–1024. doi: 10.1007/s11745-001-0812-7. [DOI] [PubMed] [Google Scholar]
  • 2.Stubbs C.D., Smith A.D. The Modification of Mammalian Membrane Polyunsaturated Fatty Acid Composition in Relation to Membrane Fluidity and Function. Biochim. Biophys. Acta. 1984;779:89–137. doi: 10.1016/0304-4157(84)90005-4. [DOI] [PubMed] [Google Scholar]
  • 3.Murphy M.G. Dietary Fatty Acids and Membrane Function. J. Nutr. Biochem. 1990;1:68–79. doi: 10.1016/0955-2863(90)90052-M. [DOI] [PubMed] [Google Scholar]
  • 4.Grimble R.F. Dietary Lipids and the Inflammatory Response. Proc. Nutr. Soc. 1998;57:535–542. doi: 10.1079/PNS19980078. [DOI] [PubMed] [Google Scholar]
  • 5.Miles E.A., Calder P.C. Modulation of Immune Function by Dietary Fatty Acids. Proc. Nutr. Soc. 1998;57:277–292. doi: 10.1079/PNS19980042. [DOI] [PubMed] [Google Scholar]
  • 6.Gibney M.J., Hunter B. The Effects of Short- and Long-Term Supplementation with Fish Oil on the Incorporation of n−3 Polyunsaturated Fatty Acids into Cells of the Immune System in Healthy Volunteers. Eur. J. Clin. Nutr. 1993;47:255–259. [PubMed] [Google Scholar]
  • 7.Sperling R.I., Benincaso A.I., Knoell C.T., Larkin J.K., Austen K.F., Robinson D.R. Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Phosphoinositide Formation and Chemotaxis in Neutrophils. J. Clin. Investig. 1993;91:651–660. doi: 10.1172/JCI116245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Lewis R.A., Austen K.F., Soberman R.J. Leukotrienes and Other Products of the 5-Lipoxygenase Pathway: Biochemistry and Relation to Pathobiology in Human Diseases. N. Engl. J. Med. 1990;323:645–655. doi: 10.1056/NEJM199009063231006. [DOI] [PubMed] [Google Scholar]
  • 9.Tilley S.L., Coffman T.M., Koller B.H. Mixed Messages: Modulation of Inflammation and Immune Responses by Prostaglandins and Thromboxanes. J. Clin. Investig. 2001;108:15–23. doi: 10.1172/JCI200113416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kinsella J.E., Lokesh B., Broughton S., Whelan J. Dietary Polyunsaturated Fatty Acids and Eicosanoids: Potential Effects on the Modulation of Inflammatory and Immune Cells: An Overview. Nutrition. 1990;6:24–44. [PubMed] [Google Scholar]
  • 11.Levy B.D., Clish C.B., Schmidt B., Gronert K., Serhan C.N. Lipid Mediator Class Switching During Acute Inflammation: Signals in Resolution. Nat. Immunol. 2001;2:612–619. doi: 10.1038/89759. [DOI] [PubMed] [Google Scholar]
  • 12.Vachier I., Chanez P., Bonnans C., Godard P., Bousquet J., Chavis C. Endogenous Anti-Inflammatory Mediators from Arachidonate in Human Neutrophils. Biochem. Biophys. Res. Commun. 2002;290:219–224. doi: 10.1006/bbrc.2001.6155. [DOI] [PubMed] [Google Scholar]
  • 13.Gewirtz A.T., Collier-Hyams L.S., Young A.N., Kucharzik T., Guilford W.J., Parkinson J.F., Williams I.R., Neish A.S., Madara J.L. Lipoxin A4 Analogs Attenuate Induction of Intestinal Epithelial Proinflammatory Gene Expression and Reduce the Severity of Dextran Sodium Sulfate-Induced Colitis. J. Immunol. 2002;168:5260–5267. doi: 10.4049/jimmunol.168.10.5260. [DOI] [PubMed] [Google Scholar]
  • 14.Obata T., Nagakura T., Masaki T., Maekawa K., Yamashita K. Eicosapentaenoic Acid Inhibits Prostaglandin D2 Generation by Inhibiting Cyclo-Oxygenase-2 in Cultured Human Mast Cells. Clin. Exp. Allergy. 1999;29:1129–1135. doi: 10.1046/j.1365-2222.1999.00604.x. [DOI] [PubMed] [Google Scholar]
  • 15.Curtis C.L., Hughes C.E., Flannery C.R., Little C.B., Harwood J.L., Caterson B. n−3 Fatty Acid Specifically Modulate Catabolic Factors Involved in Articular Cartilage Degradation. J. Biol. Chem. 2000;275:721–724. doi: 10.1074/jbc.275.2.721. [DOI] [PubMed] [Google Scholar]
  • 16.Curtis C.L., Rees S.G., Little C.B., Flannery C.R., Hughes C.E., Wilson C., Dent C.M., Otterness I.G., Harwood J.L., Caterson B. Pathologic Indicators of Degradation and Inflammation in Human Osteoarthritic Cartilage Are Abrogated by Exposure to n−3 Fatty Acids. Arthritis Rheum. 2002;46:1544–1553. doi: 10.1002/art.10305. [DOI] [PubMed] [Google Scholar]
  • 17.Endres S., Ghorbani R., Kelley V.E., Georgilis K., Lonnemann G., van der Meer J.M.W., Cannon J.G., Rogers T.S., Klempner M.S., Weber P.C., Schaeffer E.J., Wolff S.M., Dinarello C.A. The Effect of Dietary Supplementation with n−3 Polyunsaturated Fatty Acids on the Synthesis of Interleukin-1 and Tumor Necrosis Factor by Mononuclear Cells. N. Engl. J. Med. 1989;320:265–271. doi: 10.1056/NEJM198902023200501. [DOI] [PubMed] [Google Scholar]
  • 18.Meydani S.N., Lichtenstein A.H., Cornwall S., Meydani M., Goldin B.R., Rasmussen H., Dinarello C.A., Schaefer E.J. Immunologic Effects of National Cholesterol Education Panel Step-2 Diets With and Without Fish-Derived n−3 Fatty Acid Enrichment. J. Clin. Invest. 1993;92:105–113. doi: 10.1172/JCI116537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Caughey G.E., Mantzioris E., Gibson R.A., Cleland L.G., James M.J. The Effect on Human Tumor Necrosis Factor α and Interleukin 1β Production of Diets Enriched in n−3 Fatty Acids from Vegetable Oil or Fish Oil. Am. J. Clin. Nutr. 1996;63:116–122. doi: 10.1093/ajcn/63.1.116. [DOI] [PubMed] [Google Scholar]
  • 20.Lee T.H., Hoover R.L., Williams J.D., Sperling R.I., Ravalese J., Spur B.W., Robinson D.R., Corey E.J., Lewis R.A., Austen K.F. Effects of Dietary Enrichment with Eicosapentaenoic Acid and Docosahexaenoic Acid on in vitro Neutrophil and Monocyte Leukotriene Generation and Neutrophil Function. N. Engl. J. Med. 1985;312:1217–1224. doi: 10.1056/NEJM198505093121903. [DOI] [PubMed] [Google Scholar]
  • 21.Serhan C.N., Clish C.B., Brannon J., Colgan S.P., Gronert K., Chiang N. Anti-Inflammatory Lipid Signals Generated From Dietary n−3 Fatty Acids via Cyclooxygenase-2 and Transcellular Processing: A Novel Mechanism for NSAID and n−3 PUFA Therapeutic Actions. J. Physiol. Pharmacol. 2000;4:643–654. [PubMed] [Google Scholar]
  • 22.Calder P.C. n−3 Polyunsaturated Fatty Acids and Cytokine Production in Health and Disease. Ann. Nutr. Metab. 1997;41:203–234. doi: 10.1159/000177997. [DOI] [PubMed] [Google Scholar]
  • 23.de Caterina R., Cybulsky M.I., Clinton S.K., Gimbrone M.A., Libby P. The Omega-3 Fatty Acid Docosahexaenoate Reduces Cytokine-Induced Expression of Proatherogenic and Proinflammatory Proteins in Human Endothelial Cells. Arterioscler. Thromb. 1994;14:1829–1836. doi: 10.1161/01.atv.14.11.1829. [DOI] [PubMed] [Google Scholar]
  • 24.Khalfoun B., Thibault F., Watier H., Bardos P., Lebranchu Y. Docosahexaenoic and Eicosapentaenoic Acids Inhibit in vitro Human Endothelial Cell Production of Interleukin-6. Adv. Exp. Biol. Med. 1997;400:589–597. [PubMed] [Google Scholar]
  • 25.Chu A.J., Walton M.A., Prasad J.K., Seto A. Blockade by Polyunsaturated n−3 Fatty Acids of Endotoxin-Induced Monocytic Tissue Factor Activation Is Mediated by the Depressed Receptor Expression in THP-1 Cells. J. Surg. Res. 1999;87:217–224. doi: 10.1006/jsre.1999.5762. [DOI] [PubMed] [Google Scholar]
  • 26.Billiar T., Bankey P., Svingen B., Curran R.D., West M.A., Holman R.T., Simmons R.L., Cerra F.B. Fatty Acid Uptake and Kupffer Cell Function: Fish Oil Alters Eicosanoid and Monokine Production to Endotoxin Stimulation. Surgery. 1988;104:343–349. [PubMed] [Google Scholar]
  • 27.Renier G., Skamene E., de Sanctis J., Radzioch D. Dietary n−3 Polyunsaturated Fatty Acids Prevent the Development of Atherosclerotic Lesions in Mice: Modulation of Macrophage Secretory Activities. Arterioscler. Thomb. 1993;13:1515–1524. doi: 10.1161/01.atv.13.10.1515. [DOI] [PubMed] [Google Scholar]
  • 28.Yaqoob P., Calder P.C. Effects of Dietary Lipid Manipulation upon Inflammatory Mediator Production by Murine Macrophages. Cell. Immunol. 1995;163:120–128. doi: 10.1006/cimm.1995.1106. [DOI] [PubMed] [Google Scholar]
  • 29.Sadeghi S., Wallace F.A., Calder P.C. Dietary Lipids Modify the Cytokine Response to Bacterial Lipopolysaccharide in Mice. Immunology. 1999;96:404–410. doi: 10.1046/j.1365-2567.1999.00701.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Meydani S.N., Endres S., Woods M.M., Goldin B.R., Soo C., Morrill-Labrode A., Dinarello C., Gorbach S.L. Oral (n−3) Fatty Acid Supplementation Suppresses Cytokine Production and Lymphocyte Proliferation: Comparison Between Young and Older Women. J. Nutr. 1991;121:547–555. doi: 10.1093/jn/121.4.547. [DOI] [PubMed] [Google Scholar]
  • 31.Gallai V., Sarchielli P., Trequattrini A., Franceschini M., Floridi A., Firenze C., Alberti A., Di Benedetto D., Stragliotto E. Cytokine Secretions and Eicosanoid Production in the Peripheral Blood Mononuclear Cells of MS Patients Undergoing Dietary Supplementation with n−3 Polyunsaturated Fatty Acids. J. Neuroimmunol. 1993;56:143–153. doi: 10.1016/0165-5728(94)00140-J. [DOI] [PubMed] [Google Scholar]
  • 32.Calder P.C., Bond J.A., Harvey D.J., Gordon S., Newsholme E.A. Uptake of Saturated and Unsaturated Fatty Acids into Macrophage Lipids and Their Effect upon Macrophage Adhesion and Phagocytosis. Biochem. J. 1990;269:807–814. doi: 10.1042/bj2690807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Kim D.N., Schmee J., Thomas W.A. Dietary Fish Oil Added to a Hyperlipidemic Diet for Swine Results in Reduction in the Excessive Number of Monocytes Attached to the Arterial Endothelium. Atherosclerosis. 1995;81:209–216. doi: 10.1016/0021-9150(90)90068-T. [DOI] [PubMed] [Google Scholar]
  • 34.de Caterina R., Libby P. Control of Endothelial Leukocyte Adhesion Molecules by Fatty Acid. Lipids. 1996;31:S57–S63. doi: 10.1007/BF02637052. [DOI] [PubMed] [Google Scholar]
  • 35.Hughes D.A., Southon S., Pinder A.C. (n−3) Polyunsaturated Fatty Acids Modulate the Expression of Functionally Associated Molecules on Human Monocytes in vitro. J. Nutr. 1996;126:603–610. doi: 10.1093/jn/126.3.603. [DOI] [PubMed] [Google Scholar]
  • 36.Miles E.A., Wallace F.A., Calder P.C. Dietary Fish Oil Reduces Intercellular Adhesion Molecule 1 and Scavenger Receptor Expression on Murine Macrophages. Atherosclerosis. 2000;152:43–50. doi: 10.1016/S0021-9150(99)00446-3. [DOI] [PubMed] [Google Scholar]
  • 37.Hughes D.A., Pinder A.C., Piper Z., Johnson I.T., Lund E.K. Fish Oil Supplementation Inhibits the Expression of Major Histocompatibility Complex Class II Molecules and Adhesion Molecules on Human Monocytes. Am. J. Clin. Nutr. 1996;63:267–272. doi: 10.1093/ajcn/63.2.267. [DOI] [PubMed] [Google Scholar]
  • 38.Miles E.A., Thies F., Wallace F.A., Powell J.R., Hirst T.L., Newsholme E.A., Calder P.C. Influence of Age and Dietary Fish Oil on Plasma Soluble Adhesion Molecule Concentrations. Clin. Sci. 2001;100:91–100. doi: 10.1042/CS20000198. [DOI] [PubMed] [Google Scholar]
  • 39.Chandrasekar B., Fernandes G. Decreased Proinflammatory Cytokines and Increased Antioxidant Enzyme Gene Expression by ω-3 Lipids in Murine Lupus Nephritis. Biochem. Biophys. Res. Commun. 1994;200:893–898. doi: 10.1006/bbrc.1994.1534. [DOI] [PubMed] [Google Scholar]
  • 40.Robinson D.R., Urakaze M., Huang R., Taki H., Sugiyama E., Knoell C.T., Xu L., Yeh E.T.H., Auron P.E. Dietary Marine Lipids Suppress Continuous Expression of Interleukin-1β Gene Expression. Lipids. 1996;31:S23–S31. doi: 10.1007/BF02637046. [DOI] [PubMed] [Google Scholar]
  • 41.Christman J.W., Lancaster L.H., Blackwell T.S. Nuclear Factor-κB: A Pivotal Role in Systemic Inflammatory Response Syndrome and New Target for Therapy. Int. Care Med. 1998;24:1131–1138. doi: 10.1007/s001340050735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Chen F., Castranova V., Shi X., Demers L.M. New Insights into the Role of Nuclear Factor-κB, a Ubiquitous Transcription Factor in the Initiation of Diseases. Clin. Chem. 1999;45:7–17. [PubMed] [Google Scholar]
  • 43.Calder P.C. Dietary Modification of Inflammation with Lipids. Proc. Nutr. Soc. 2002;61:345–358. doi: 10.1079/PNS2002186. [DOI] [PubMed] [Google Scholar]
  • 44.Karin M., Ben-Neriah Y. Phosphorylation Meets Ubiquination: The Control of NF-κB Activity. Annu. Rev. Immunol. 2000;18:621–663. doi: 10.1146/annurev.immunol.18.1.621. [DOI] [PubMed] [Google Scholar]
  • 45.Karin M., Delhase M. The IκB Kinase (IκK) and NF-κB: Key Elements of Proinflammatory Signalling. Semin. Immunol. 2000;12:85–98. doi: 10.1006/smim.2000.0210. [DOI] [PubMed] [Google Scholar]
  • 46.Xi S., Cohen D., Barve S., Chen L.H. Fish Oil Suppressed Cytokines and Nuclear Factor κB Induced by Murine AIDS Virus Infection. Nutr. Res. 2001;21:865–878. doi: 10.1016/S0271-5317(01)00290-1. [DOI] [Google Scholar]
  • 47.Chen L.H., Zhao Y. Eicosapentaenoic Acid Decreases Lipopolysaccharide-Stimulated Tumor Necrosis Factor-α Expression by Inhibiting Nuclear Factor κB Activation. FASEB J. 2001;15:A258–A258. [Google Scholar]
  • 48.Ross J.A., Moses A.G.W., Fearon K.C.H. The Anti-Catabolic Effects of n−3 Fatty Acids. Curr. Opin. Clin. Nutr. Metab. Care. 1999;2:219–226. doi: 10.1097/00075197-199905000-00005. [DOI] [PubMed] [Google Scholar]
  • 49.Schoonjans K., Staels B., Auwerx J. The Peroxisome Proliferator Activated Receptor (PPARs) and Their Effects on Lipid Metabolism and Adipocyte Differentiation. Biochim. Biophys. Acta. 1996;1302:93–109. doi: 10.1016/0005-2760(96)00066-5. [DOI] [PubMed] [Google Scholar]
  • 50.Chinetti G., Griglio S., Antonucci M., Torra I.P., Delerive P., Majd Z., Fruchart J.C., Chapman J., Najib J., Staels B. Activation of Peroxisome-Activated Receptors α and γ Induces Apoptosis of Human Monocyte-Derived Macrophages. J. Biol. Chem. 1998;273:25573–25580. doi: 10.1074/jbc.273.40.25573. [DOI] [PubMed] [Google Scholar]
  • 51.Ricote M., Li A.C., Wilson T.M., Kelly C.J., Glass C.K. The Peroxisome Proliferator-Activated Receptor-γ Is a Negative Regulator of Macrophage Activation. Nature. 1998;391:79–82. doi: 10.1038/34178. [DOI] [PubMed] [Google Scholar]
  • 52.Kleiwer S.A., Lenhard J.M., Willson T.M., Patel I., Morris D.C., Lehman J.M. A Prostaglandin J2 Metabolite Binds Peroxisome Proliferator-Activated Receptor γ and Promotes Adipocyte Differentiation. Cell. 1995;83:813–819. doi: 10.1016/0092-8674(95)90194-9. [DOI] [PubMed] [Google Scholar]
  • 53.Devchand P.R., Keller H., Peters J.M., Vazquez M., Gonzalez F.J., Wahli W. The PPARγ-Leukotriene B4 Pathway to Inflammation Control. Nature. 1996;384:39–43. doi: 10.1038/384039a0. [DOI] [PubMed] [Google Scholar]
  • 54.Jiang C.Y., Ting A.T., Seed B. PPAR-γ Agonists Inhibit Production of Monocyte Inflammatory Cytokines. Nature. 1998;391:82–86. doi: 10.1038/35154. [DOI] [PubMed] [Google Scholar]
  • 55.Poynter M.E., Daynes R.A. Peroxisome Proliferator-Actived Receptor α Activation Modulates Cellular Redox Status, Represses Nuclear Factor κB Signalling, and Reduces Inflammatory Cytokine Production in Aging. J. Biol. Chem. 1998;273:32833–32841. doi: 10.1074/jbc.273.49.32833. [DOI] [PubMed] [Google Scholar]
  • 56.Jackson S.M., Parhami F., Xi X.-P., Berlinger J.A., Hsueh W.A., Law R.E., Demer L.L. Peroxisome Proliferator-Activated Receptor Activators Target Human Endothelial Cells to Inhibit Leukocyte-Endothelial Cell Interaction, Arterioscler. Thromb. Vasc. Biol. 1999;19:2094–2104. doi: 10.1161/01.atv.19.9.2094. [DOI] [PubMed] [Google Scholar]
  • 57.Marx N., Sukhova G.K., Collins T., Libby P., Plutzky J. PPARα Activators Inhibit Cytokine-Induced Vascular Cell Adhesion Molecule-1 Expression in Human Endothelial Cells. Circulation. 1999;99:3125–3131. doi: 10.1161/01.cir.99.24.3125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Takano H., Nagai T., Asakawa M., Toyozaki T., Oka T., Komuro I., Saito T., Masuda Y. Peroxisome Proliferator-Receptor Activators Inhibit Lipopolysaccharide-Induced Tumor Necrosis Factor-Alpha Expression in Neonatal Rat Cardiac Myocytes. Circ. Res. 2000;87:596–602. doi: 10.1161/01.res.87.7.596. [DOI] [PubMed] [Google Scholar]
  • 59.Wang P., Anderson P.O., Chen S.W., Paulsson K.M., Sjogren H.O., Li S.L. Inhibition of the Transcription Factors AP-1 and NF-κB in CD4 T Cells by Peroxisome Proliferator-Activated Receptor γ Ligands. Int. Immunopharmacol. 2001;1:803–812. doi: 10.1016/S1567-5769(01)00015-7. [DOI] [PubMed] [Google Scholar]
  • 60.Xu X., Otsuki M., Saito H., Sumitani S., Yamamoto H., Asanuma N., Kouh A.A., Kasayama S. PFARα and GR Differentially Down-Regulate the Expression of Nuclear Factor-κB-Responsive Genes in Vascular Endothelial Cells. Endocrinology. 2001;142:3332–3339. doi: 10.1210/en.142.8.3332. [DOI] [PubMed] [Google Scholar]
  • 61.Chinetti G., Fruchart J.C., Staels B. Peroxisome Proliferator-Activated Receptors (PPARs): Nuclear Receptors at the Crossroads Between Lipid Metabolism and Inflammation. Inflamm. Res. 2000;49:497–505. doi: 10.1007/s000110050622. [DOI] [PubMed] [Google Scholar]
  • 62.Delerive P., Fruchart J.C., Staels B. Peroxisome Proliferator-Activated Receptors in Inflammation Control. J. Endocrinol. 2001;169:453–459. doi: 10.1677/joe.0.1690453. [DOI] [PubMed] [Google Scholar]
  • 63.Donnellan C.E., Tadayyon M., Briscoe C., Arch J., Calder P.C. The Effect of Dietary Fatty Acids on the Expression of Genes Involved in Lipid Handling. Proc. Nutr. Soc. 2000;59:111A–111A. [Google Scholar]
  • 64.Hwang D., Rhee S.H. Receptor-Mediated Signalling Pathways: Potential Targets of Modulation by Dietary Fatty Acids. Am. J. Clin. Nutr. 1999;70:545–556. doi: 10.1093/ajcn/70.4.545. [DOI] [PubMed] [Google Scholar]
  • 65.Lo C.J., Chiu K.C., Fu M.J., Chu A., Helton S. Fish Oil Modulates Macrophages P44/42 Mitogen-Activated Protein Kinase Activity Induced by Lipopolysaccharide. J. Parenter. Enteral Nutr. 2000;24:159–163. doi: 10.1177/0148607100024003159. [DOI] [PubMed] [Google Scholar]
  • 66.Panayi G.S. Targeting of Cells Involved in the Pathogenesis of Rheumatoid Arthritis. Rheumatology. 1999;38(Suppl. 2):8–10. [PubMed] [Google Scholar]
  • 67.Feldmann M., Maini R.N. The Role of Cytokines in the Pathogenesis of Rheumatoid Arthritis. Rheumatology. 1999;38(Suppl. 2):3–7. [PubMed] [Google Scholar]
  • 68.Feldmann M., Brennan F.M., Maini R.N. Role of Cytokines in Rheumatoid Arthritis. Annu. Rev. Immunol. 1996;14:397–440. doi: 10.1146/annurev.immunol.14.1.397. [DOI] [PubMed] [Google Scholar]
  • 69.Sano H., Hla T., Maier J.A.M., Crofford L.J., Case J.P., Maciag T., Wilder R.L. In vivo Cyclooxygenase Expression in Synovial Tissues of Patients with Rheumatoid Arthritis and Osteoarthritis and Rats with Adjuvant and Streptococcal Cell Wall Arthritis. J. Clin. Investig. 1992;89:97–108. doi: 10.1172/JCI115591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Sperling R.I. Eicosanoids in Rheumatoid Arthritis. Rheum. Dis. Clin. N. Am. 1995;21:741–758. [PubMed] [Google Scholar]
  • 71.Faull R.J. Adhesion Molecules in Health and Disease. Aust. N.Z.J. Med. 1995;25:720–730. doi: 10.1111/j.1445-5994.1995.tb02861.x. [DOI] [PubMed] [Google Scholar]
  • 72.Leslie C.A., Gonnerman W.A., Ullman M.D., Hayes K.C., Franzblau C., Cathcart E.S. Dietary Fish Oil Modulates Macrophage Fatty Acids and Decreases Arthritis Susceptibility in Mice. J. Exp. Med. 1985;162:1336–1349. doi: 10.1084/jem.162.4.1336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Volker D.H., FitzGerald P.E.B., Garg M.L. The Eicosapentaenoic to Docosahexaenoic Acid Ratio of Diets Affects the Pathogenesis of Arthritis in Lew/SSN Rats. J. Nutr. 2000;130:559–565. doi: 10.1093/jn/130.3.559. [DOI] [PubMed] [Google Scholar]
  • 74.Calder P.C. n−3 Fatty Acids and Rheumatoid Arthritis. In: Ransley J.K., Donnelly J.K., Read N.W., editors. Food and Nutritional Supplements in Health and Disease. London: Springer Verlag; 2001. pp. 175–197. [Google Scholar]
  • 75.Calder P.C., Zurier R.B. Polyunsaturated Fatty Acids and Rheumatoid Arthritis. Curr. Opin. Clin. Nutr. Metab. Care. 2001;4:115–121. doi: 10.1097/00075197-200103000-00006. [DOI] [PubMed] [Google Scholar]
  • 76.Cleland L.G., James M.J. Fish Oil and Rheumatoid Arthritis: Anti-Inflammatory and Collateral Health Benefits. J. Rheumatol. 2000;27:2305–2307. [PubMed] [Google Scholar]
  • 77.Knapp H.R. Omega-3 Fatty-Acids in Respiratory Diseases—A Review. J. Am. Coll. Nutr. 1995;14:18–23. doi: 10.1080/07315724.1995.10718468. [DOI] [PubMed] [Google Scholar]
  • 78.Calder P.C., Miles E.A. Fatty Acids and Atopic Disease. Pediatr. Allergy Immunol. 2000;11:29–36. doi: 10.1034/j.1399-3038.2000.00508.x. [DOI] [PubMed] [Google Scholar]
  • 79.Broughton K.S., Johnson C.S., Pace B.K., Liebman M., Kleppinger K.M. Reduced Asthma Symptoms with n−3 Fatty Acid Ingestion Are Related to 5-Series Leukotriene Production. Am. J. Clin. Nutr. 1997;65:1011–1017. doi: 10.1093/ajcn/65.4.1011. [DOI] [PubMed] [Google Scholar]
  • 80.Burney P.G.J., Chinn S., Rona R.J. Has the Prevalence of Asthma Increased in Children? Evidence from the National Survey of Health and Growth 1973–1986. Br. Med. J. 1990;300:1306–1310. doi: 10.1136/bmj.300.6735.1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Heinrich J., Hoelscher B., Frye C., Meyer I., Wjst M., Wichmann H.E. Trends in Prevalence of Atopic Diseases and Allergic Sensitization in Children in Eastern Germany. Eur. Resp. J. 2002;19:1040–1046. doi: 10.1183/09031936.02.00261802. [DOI] [PubMed] [Google Scholar]
  • 82.Romagnani S. The Role of Lymphocytes in Allergic Disease. J. Allergy Clin. Immunol. 2000;105:399–408. doi: 10.1067/mai.2000.104575. [DOI] [PubMed] [Google Scholar]
  • 83.Hodge L., Peat J.K., Salome C. Increased Consumption of Polyunsaturated Oils May Be a Cause of Increased Prevalence of Childhood Asthma. Aust. N.Z. J. Med. 1994;24:727–727. doi: 10.1111/j.1445-5994.1994.tb01793.x. [DOI] [PubMed] [Google Scholar]
  • 84.Black P.N., Sharp S. Dletary Fat and Asthma: Is There a Connection? Eur. Resp. J. 1997;10:6–12. doi: 10.1183/09031936.97.10010006. [DOI] [PubMed] [Google Scholar]
  • 85.Kankaanpaa P., Sutas Y., Salminen S., Lichtenstein A., Isolauri E. Dietary Fatty Acids and Allergy. Ann. Med. 1999;31:282–287. doi: 10.3109/07853899908995891. [DOI] [PubMed] [Google Scholar]
  • 86.Yu G., Kjellman N.I., Bjorksten B. Phospholipid Fatty Acids in Cord Blood: Family History and Development of Allergy. Acta Paediatr. 1996;85:679–683. doi: 10.1111/j.1651-2227.1996.tb14124.x. [DOI] [PubMed] [Google Scholar]
  • 87.Duchen K., Yu G., Bjorksten B. Atopic Sensitization During the First Year of Life in Relation to Long-Chain Polyunsaturated Fatty Acid Levels in Human Milk. Pediatr. Res. 1998;44:478–484. doi: 10.1203/00006450-199810000-00003. [DOI] [PubMed] [Google Scholar]
  • 88.Yu G., Bjorksten B. Polyunsaturated Fatty Acids in School Children in Relation to Allergy and Serum IgE Levels. Pediatr. Allergy Immunol. 1998;8:133–138. doi: 10.1111/j.1399-3038.1998.tb00359.x. [DOI] [PubMed] [Google Scholar]
  • 89.Schwartz J., Weiss S.T. The Relationship of Dietary Fish Intake to Level of Pulmonary Function in the First National Health and Nutrition Survey. Eur. Resp. J. 1994;7:1821–1824. doi: 10.1183/09031936.94.07101821. [DOI] [PubMed] [Google Scholar]
  • 90.Schwartz J., Weiss S.T. Dietary Factors and Their Relation to Respiratory Symptoms: The Second National Health and Nutrition Survey. Am. J. Epidemiol. 1990;132:67–76. doi: 10.1093/oxfordjournals.aje.a115644. [DOI] [PubMed] [Google Scholar]
  • 91.Hodge L., Salome C.M., Peat J.K., Haby M.M., Xuan W., Woodcock A.J. Consumption of Oily Fish and Childhood Asthma Risk. Med. J. Aust. 1996;164:137–140. doi: 10.5694/j.1326-5377.1996.tb122010.x. [DOI] [PubMed] [Google Scholar]
  • 92.Dunder T., Kuikka L., Turtinen J., Rasanen L., Uhari M. Diet, Serum Fatty Acids, and Atopic Diseases in Childhood. Allergy. 2001;56:425–428. doi: 10.1034/j.1398-9995.2001.056005425.x. [DOI] [PubMed] [Google Scholar]
  • 93.Jones A., Miles E., Warner J., Colwell B., Bryant T., Warner J. Fetal Peripheral Blood Mononuclear Cell Proliferative Responses to Mitogenic and Allergenic Stimuli During Gestation. Pediatr. Allergy Immunol. 1996;7:109–116. doi: 10.1111/j.1399-3038.1996.tb00117.x. [DOI] [PubMed] [Google Scholar]
  • 94.Cannon J.G., Tompkins R.G., Gelfrand J.A., Michie H.R., Stanford G.G., Van der Meer J.W., Endres S., Lonnemann G., Corsetti J., Chernow B., Wilmore D.W., Wolff S.M., Burke J.F., Dinarello C.A. Circulating Interleukin-1 and Tumor Necrosis Factor in Septic Shock and Experimental Endotoxin Fever. J. Infect. Dis. 1990;161:79–84. doi: 10.1093/infdis/161.1.79. [DOI] [PubMed] [Google Scholar]
  • 95.Arnalich F., Garcia-Palomero E., Lopez J., Jimenez M., Madero R., Renart J., Vazquez J.J., Montiel C. Predictive Value of Nuclear Factor κB Activity and Plasma Cytokine Levels in Patients with Sepsis. Infect. Immunol. 2000;68:1942–1945. doi: 10.1128/IAI.68.4.1942-1945.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.Vervloet M.G., Thijs L.G., Hack C.E. Derangements of Coagulation and Fibrinolysis in Critically Ill Patients with Sepsis and Septic Shock. Semin. Thromb. Hemost. 1998;24:33–44. doi: 10.1055/s-2007-995821. [DOI] [PubMed] [Google Scholar]
  • 97.Grbic J.T., Mannick J.A., Gough D.B., Rodrick M.L. The Role of Prostaglandin E2 in Immune Suppression Following Injury. Ann. Surg. 1991;214:253–263. doi: 10.1097/00000658-199109000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Ertel W., Morrison M.H., Meldrum D.R., Ayala A., Chaudry I.H. Ibuprofen Restores Cellular Immunity and Decreases Susceptibility to Sepsis Following Hemorrhage. J. Surg. Res. 1992;53:55–61. doi: 10.1016/0022-4804(92)90013-P. [DOI] [PubMed] [Google Scholar]
  • 99.Tashiro T., Yamamori H., Takagi K., Hayashi N., Furukawa K., Nakajima N. n−3 Versus n−6 Polyunsaturated Fatty Acids in Critical Illness. Nutrition. 1998;14:551–553. doi: 10.1016/S0899-9007(98)00048-3. [DOI] [PubMed] [Google Scholar]
  • 100.Hayashi N., Tashiro T., Yamamori H., Takagi K., Morishima Y., Otsubo Y., Sugiura T., Furukawa K., Nitta H., Nakajima N., Suzuki N., Ito I. Effects of Intravenous Omega-3 and Omega-6 Fat Emulsion on Cytokine Production and Delayed Type Hypersensitivity in Burned Rats Receiving Total Parenteral Nutrition. J. Parenter. Enteral Nutr. 1998;22:363–367. doi: 10.1177/0148607198022006363. [DOI] [PubMed] [Google Scholar]
  • 101.Wachtler P., Konig W., Senkal M., Kemen M., Koller M. Influence of a Total Parenteral Nutrition Enriched with ω-3 Fatty Acids on Leukotriene Synthesis of Peripheral Leukocytes and Systemic Cytokine Levels in Patients with Major Surgery. J. Trauma. 1997;42:191–198. doi: 10.1097/00005373-199702000-00004. [DOI] [PubMed] [Google Scholar]
  • 102.Weiss G., Meyer F., Matthies B., Pross M., Koenig W., Lippert H. Immunomodulation by Perioperative Administration of n−3 Fatty Acids. Br. J. Nutr. 2002;87:S89–S94. doi: 10.1079/BJN2001461. [DOI] [PubMed] [Google Scholar]
  • 103.Heyland D.K., Novak F., Drover J.W., Jain A., Su X.Y., Suchner U. Should Immunonutrition Become Routine in Critically Ill Patients? A Systematic Review of the Evidence. J. Am. Med. Assoc. 2001;286:944–953. doi: 10.1001/jama.286.8.944. [DOI] [PubMed] [Google Scholar]
  • 104.Braga M., Vignali A., Gianotti L., Cestari A., Profili M., Di Carlo V. Immune and Nutritional Effects of Early Enteral Nutrition After Major Abdominal Operations. Eur. J. Surg. 1996;162:105–112. [PubMed] [Google Scholar]
  • 105.Braga M., Gianotti L., Radaelli G., Vignali A., Mari G., Gentilini O., Di Carlo V. Perioperative Immunonutrition in Patients Undergoing Cancer Surgery. Arch. Surg. 1999;134:428–433. doi: 10.1001/archsurg.134.4.428. [DOI] [PubMed] [Google Scholar]
  • 106.Gianotti L., Braga M., Fortis C., Soldini L., Vignali A., Colombo S., Radaelli G., Di Carlo V. A Prospective, Randomized Clinical Trial on Perioperative Feeding with an Arginine-, Omega-3 Fatty Acid-, and RNA-Enriched Enteral Diet: Effect on Host Response and Nutritional Status. J. Parenter. Enteral Nutr. 1999;23:314–320. doi: 10.1177/0148607199023006314. [DOI] [PubMed] [Google Scholar]
  • 107.Tepaske R., te Velthuis H., Oudemans-van Straaten M., Heisterkamp S.H., van Deventer S.J.H., Ince C., Eysman L., Keseciogu J. Effect of Preoperative Oral Immune-Enhancing Nutritional Supplement on Patients at Risk of Infection After Cardiac Surgery: A Randomised Placebo-Controlled Trial. Lancet. 2001;358:696–701. doi: 10.1016/S0140-6736(01)05836-6. [DOI] [PubMed] [Google Scholar]
  • 108.Gadek J.E., DeMichele S.J., Karlstad M.D., Pacht E.R., Donahoe M., Albertson T.E., Van Hoozen C., Wennberg A.K., Nelson J., Noursalehi M., the Enteral Nutrition in ARDS Study Group Effect of Enteral Feeding with Eicosapentaenoic Acid, γ-Linolenic Acid, and Antioxidants in Patients with Acute Respiratory Distress Syndrome. Crit. Care Med. 1999;27:1409–1420. doi: 10.1097/00003246-199908000-00001. [DOI] [PubMed] [Google Scholar]

Articles from Lipids are provided here courtesy of Nature Publishing Group

RESOURCES