Skip to main content

Advertisement

SpringerLink
Log in

Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective

  • Review
  • Published:
Intensive Care Medicine Aims and scope Submit manuscript

Abstract

Introduction

Fish oil-based nutrition is protective in severe critical care conditions. Regulation of the activity of transcription factor NF-κB is an important therapeutic effect of the major omega-3 fatty acids in fish oil, eicosapentaenoic and docosahexaenoic acid (EPA and DHA).

Methods and results

Using the articles obtained by a Pubmed research, this article reviews three aspects of NF-κB/inflammatory inhibition by fish oil. (1) Inhibition of the NF-κB pathway at several subsequent steps: extracellular, free omega-3 inhibits the activation of the Toll-like receptor 4 by endotoxin and free saturated fatty acids. In addition, EPA/DHA blocks the signaling cascade between Toll-like/cytokine receptors and the activator of NF-κB, IKK. Oxidized omega-3 also interferes with the initiation of transcription by NF-κB. (2) The altered profile of lipid mediators generated during inflammation, with production of the newly identified, DHA-derived inflammation-resolving mediator classes (in addition to the formation of less pro-inflammatory eicosanoids from EPA). Resolvin D1 and Protectin D1 are potent, endogenous, DHA-derived lipid mediators that attenuate neutrophil migration and tissue injury in peritonitis and ischemia-reperfusion injury. Their production is increased in the later stages of an inflammatory response, at which time they enhance the removal of neutrophils. (3) Modulation of vagal tone with potential anti-inflammatory effects: vagal fibers innervating the viscera down-regulate inflammation by activating nicotinic receptors upon infiltrating and resident macrophages. Stimulation of the efferent vagus is therapeutic in experimental septic shock. Fish oil supplementation increases vagal tone following myocardial infarction and in experimental human endotoxinemia.

Conclusion

It remains to be shown whether these pleiotropic actions of EPA/DHA contribute to fish oil’s therapeutic effect in sepsis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Notes

  1. Fatty acids are either saturated (SatFA) or unsaturated (UnSatFA), depending on the lack of (in SatFAs) or presence of (in UnSatFAs) carbon–carbon double bond(s) [-CH=CH-]. UnSatFAs may be mono- or polyunsaturated (MUFA and PUFA). A simple biochemical description of fatty acids is Cx:y, where x designates the number of carbons in the carbon chain and y designates the number of double bonds. Very long chain PUFAs are those containing 20 or more carbons. ω-n indicates that the first double bond appears as the nth carbon–carbon bond from the methyl end.

  2. A protein that is not enzymatically active but instead mediates the formation of protein-receptor complexes responsible for post-receptor signal transduction.

  3. The structure of Lipid A is more complex than described here; a more detailed and accurate overview can be found in [15]. To be slightly more accurate, Lipid A of these GNBs is a disaccharide of glucosamine, covalently bonded to lauric or myristic acid chains; these saturated fatty acids are further bonded to lauric, myristic or palmitic acid chains.

  4. NIK is NF-κBNF-κBNF-κB-inducing kinase. It is downstream to MyD88 and activates IKK.

  5. e.g. ceramides, diacylglycerol and fatty acyl-CoAs

  6. A Saccharomyces cerevisiae PARPPARP that is recognized by TLR2. When administered at higher doses it produces lethal septic shock.

References

  1. Grimble RF (2005) Immunonutrition. Curr Opin Gastroenterol 21:216–222

    Article  PubMed  CAS  Google Scholar 

  2. Kudsk KA (2006) Immunonutrition in surgery and critical care. Annu Rev Nutr 26:463–479

    Article  PubMed  CAS  Google Scholar 

  3. Pontes-Arruda A, Aragão AM, Albuquerque JD (2006) Effects of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in mechanically ventilated patients with severe sepsis and septic shock. Crit Care Med 34:2325–2333

    Article  PubMed  CAS  Google Scholar 

  4. Singer P, Theilla M, Fisher H, Gibstein L, Grozovski E, Cohen J (2006) Benefit of an enteral diet enriched with eicosapentaenoic acid and gamma-linolenic acid in ventilated patients with acute lung injury. Crit Care Med 34:1033–1038

    Article  PubMed  CAS  Google Scholar 

  5. Heller AR, Rossler S, Litz RJ, Stehr SN, Heller SC, Koch R, Koch T (2006) Omega-3 fatty acids improve the diagnosis-related clinical outcome. Crit Care Med 34:972–979

    Article  PubMed  CAS  Google Scholar 

  6. Gadek JE, DeMichele SJ, Karlstad MD, Pacht ER, Donahoe M, Albertson TE, Van Hoozen C, Wennberg AK, Nelson JL, Noursalehi M (1999) Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group. Crit Care Med 27:1409–1420

    Article  PubMed  CAS  Google Scholar 

  7. Pontes-Arruda A, DeMichele S, Seth A, Singer P (2006) Enteral nutrition with Eicosapentaenoic acid (EPA, gamma-linolenic acid (GLA) and antioxidants in critical illness: a meta-analysis evaluation of outcome data. Crit Care Med 34:S95

    Article  Google Scholar 

  8. Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83(6 Suppl):1505S–1519S

    PubMed  CAS  Google Scholar 

  9. Arterburn LM, Hall EB, Oken H (2006) Distribution, interconversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr 83(6 Suppl):1467S–1476S

    PubMed  CAS  Google Scholar 

  10. Wanten GJ, Calder PC (2007) Immune modulation by parenteral lipid emulsions. Am J Clin Nutr 85:1171–1184

    PubMed  CAS  Google Scholar 

  11. Wendel M, Paul R, Heller AR (2007) Lipoproteins in inflammation and sepsis. II. Clinical aspects. Intensive Care Med 33:25–35

    Article  PubMed  CAS  Google Scholar 

  12. Janssens S, Beyaert R (2003) Role of Toll-like receptors in pathogen recognition. Clin Microbiol Rev 16:637–646

    Article  PubMed  CAS  Google Scholar 

  13. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365:63–78

    Article  PubMed  CAS  Google Scholar 

  14. Triantafilou M, Triantafilou K (2002) Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol 23:301–304

    Article  PubMed  CAS  Google Scholar 

  15. Raetz CR (1990) Biochemistry of endotoxins. Annu Rev Biochem 59:129–170

    Article  PubMed  CAS  Google Scholar 

  16. Liu SF, Malik AB (2006) NF-kappa B activation as a pathological mechanism of septic shock and inflammation. Am J Physiol Lung Cell Mol Physiol 290:L622–L645

    Article  PubMed  CAS  Google Scholar 

  17. Miyake K (2007) Innate immune sensing of pathogens and danger signals by cell surface Toll-like receptors. Semin Immunol 19:3–10

    Article  PubMed  CAS  Google Scholar 

  18. Fan J, Li Y, Levy RM, Fan JJ, Hackam DJ, Vodovotz Y, Yang H, Tracey KJ, Billiar TR, Wilson MA (2007) Hemorrhagic shock induces NAD(P)H oxidase activation in neutrophils: role of HMGB1-TLR4 signaling. J Immunol 178:6573–6580

    PubMed  CAS  Google Scholar 

  19. Shimamoto A, Pohlman TH, Shomura S, Tarukawa T, Takao M, Shimpo H (2006) Toll-like receptor 4 mediates lung ischemia-reperfusion injury. Ann Thorac Surg 82:2017–2023

    Article  PubMed  Google Scholar 

  20. Miller SI, Ernst RK, Bader MW (2005) LPS, TLR4 and infectious disease diversity. Nat Rev Microbiol 3:36–46

    Article  PubMed  CAS  Google Scholar 

  21. Krauss JH, Seydel U, Weckesser J, Mayer H (1989) Structural analysis of the nontoxic lipid A of Rhodobacter capsulatus 37b4. Eur J Biochem 180:519–526

    Article  PubMed  CAS  Google Scholar 

  22. Qureshi N, Takayama K, Kurtz R (1991) Diphosphoryl lipid A obtained from the nontoxic lipopolysaccharide of Rhodopseudomonas sphaeroides is an endotoxin antagonist in mice. Infect Immun 59:441–444

    PubMed  CAS  Google Scholar 

  23. Lee JY, Hwang DH (2006) The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. Mol Cells 21:174–185

    PubMed  CAS  Google Scholar 

  24. Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276:16683–16689

    Article  PubMed  CAS  Google Scholar 

  25. Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH (2003) Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res 44:479–486

    Article  PubMed  CAS  Google Scholar 

  26. Lee JY, Zhao L, Youn HS, Weatherill AR, Tapping R, Feng L, Lee WH, Fitzgerald KA, Hwang DH (2004) Saturated fatty acid activates but polyunsaturated fatty acid inhibits Toll-like receptor 2 dimerized with Toll-like receptor 6 or 1. J Biol Chem 279:16971–16979

    Article  PubMed  CAS  Google Scholar 

  27. Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116:3015–3025

    Article  PubMed  CAS  Google Scholar 

  28. Kim F, Pham M, Luttrell I, Bannerman DD, Tupper J, Thaler J, Hawn TR, Raines EW, Schwartz MW (2007) Toll like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity. Circ Res 100:1589–1596

    Article  PubMed  CAS  Google Scholar 

  29. Bursten SL, Federighi DA, Parsons P, Harris WE, Abraham E, Moore EE Jr, Moore FA, Bianco JA, Singer JW, Repine JE (1996) An increase in serum C18 unsaturated free fatty acids as a predictor of the development of acute respiratory distress syndrome. Crit Care Med 24:1129–1136

    Article  PubMed  CAS  Google Scholar 

  30. Mayer K, Gokorsch S, Fegbeutel C, Hattar K, Rosseau S, Walmrath D, Seeger W, Grimminger F (2003) Parenteral nutrition with fish oil modulates cytokine response in patients with sepsis. Am J Respir Crit Care Med 167:1321–1328

    Article  PubMed  Google Scholar 

  31. Delarue J, Magnan C (2007) Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care 10:142–148

    Article  PubMed  CAS  Google Scholar 

  32. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, Prada PO, Hirabara SM, Schenka AA, Araujo EP, Vassalo J, Curi R, Velloso LA, Saad MJ (2007) Loss-of-function mutation in TLR4 prevents diet-induced obesity and insulin resistance. Diabetes 56:1986–1998

    Article  PubMed  CAS  Google Scholar 

  33. Lo CJ, Chiu KC, Fu M, Lo R, Helton S (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF kappa B activity. J Surg Res 82:216–221

    Article  PubMed  CAS  Google Scholar 

  34. Zhao Y, Joshi-Barve S, Barve S, Chen LH (2004) Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 23:71–78

    PubMed  CAS  Google Scholar 

  35. Weldon SM, Mullen AC, Loscher CE, Hurley LA, Roche HM (2007) Docosahexaenoic acid induces an anti-inflammatory profile in lipopolysaccharide-stimulated human THP-1 macrophages more effectively than eicosapentaenoic acid. J Nutr Biochem 18:250–258

    Article  PubMed  CAS  Google Scholar 

  36. Novak TE, Babcock TA, Jho DH, Helton WS, Espat NJ (2003) NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. Am J Physiol Lung Cell Mol Physiol 284:L84–L89

    PubMed  CAS  Google Scholar 

  37. Moon DO, Kim KC, Jin CY, Han MH, Park C, Lee KJ, Park YM, Choi YH, Kim GY (2007) Inhibitory effects of eicosapentaenoic acid on lipopolysaccharide-induced activation in BV2 microglia. Int Immunopharmacol 7:222–229

    Article  PubMed  CAS  Google Scholar 

  38. Whitehouse AS, Tisdale MJ (2003) Increased expression of the ubiquitin-proteasome pathway in murine myotubes by proteolysis-inducing factor (PIF) is associated with activation of the transcription factor NF-kappaB. Br J Cancer 89:1116–1122

    Article  PubMed  CAS  Google Scholar 

  39. Chen W, Esselman WJ, Jump DB, Busik JV (2005) Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 46:4342–4347

    Article  PubMed  Google Scholar 

  40. Lo CJ, Chiu KC, Fu M, Chu A, Helton S (2000) Fish oil modulates macrophage P44/P42 mitogen-activated protein kinase activity induced by lipopolysaccharide. JPEN J Parenter Enteral Nutr 24:159–163

    Article  PubMed  CAS  Google Scholar 

  41. Babcock TA, Kurland A, Helton WS, Rahman A, Anwar KN, Espat NJ (2003) Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases. JPEN J Parenter Enteral Nutr 27:176–180

    Article  PubMed  CAS  Google Scholar 

  42. Swantek JL, Cobb MH, Geppert TD (1997) Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) is required for lipopolysaccharide stimulation of tumor necrosis factor alpha (TNF-alpha) translation: glucocorticoids inhibit TNF-alpha translation by blocking JNK/SAPK. Mol Cell Biol 17:6274–6282

    PubMed  CAS  Google Scholar 

  43. Fan H, Peck OM, Tempel GE, Halushka PV, Cook JA (2004) Toll-like receptor 4 coupled GI protein signaling pathways regulate extracellular signal-regulated kinase phosphorylation and AP-1 activation independent of NFkappaB activation. Shock 22:57–62

    Article  PubMed  CAS  Google Scholar 

  44. Hacker H, Karin M (2006) Regulation and function of IKK and IKK-related kinases. Sci STKE (357):re13

  45. De Bosscher K, Vanden Berghe W, Haegeman G (2006) Cross-talk between nuclear receptors and nuclear factor kappaB. Oncogene 25:6868–6886

    Article  PubMed  CAS  Google Scholar 

  46. Mishra A, Chaudhary A, Sethi S (2004) Oxidized omega-3 fatty acids inhibit NF-kappaB activation via a PPARalpha-dependent pathway. Arterioscler Thromb Vasc Biol 24:1621–1627

    Article  PubMed  CAS  Google Scholar 

  47. Li H, Ruan XZ, Powis SH, Fernando R, Mon WY, Wheeler DC, Moorhead JF, Varghese Z (2005) EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for a PPAR-gamma-dependent mechanism. Kidney Int 67:867–874

    Article  PubMed  CAS  Google Scholar 

  48. Sethi S (2002) Inhibition of leukocyte–endothelial interactions by oxidized omega-3 fatty acids: a novel mechanism for the anti-inflammatory effects of omega-3 fatty acids in fish oil. Redox Rep 7:369–378

    Article  PubMed  CAS  Google Scholar 

  49. Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A (2006) A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol 169:846–860

    Article  PubMed  CAS  Google Scholar 

  50. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M, Ruzickova J, Kopecky J (2006) Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetologia 49:394–397

    Article  PubMed  CAS  Google Scholar 

  51. Perez-Matute P, Perez-Echarri N, Martinez JA, Marti A, Moreno-Aliaga MJ (2007) Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-alpha. Br J Nutr 97:389–398

    Article  PubMed  CAS  Google Scholar 

  52. Neumeier M, Weigert J, Schaffler A, Wehrwein G, Muller-Ladner U, Scholmerich J, Wrede C, Buechler C (2006) Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol 79:803–808

    Article  PubMed  CAS  Google Scholar 

  53. Sell H, Dietze-Schroeder D, Eckel J (2006) The adipocyte–myocyte axis in insulin resistance. Trends Endocrinol Metab 17:416–422

    Article  PubMed  CAS  Google Scholar 

  54. Tsuchihashi H, Yamamoto H, Maeda K, Ugi S, Mori T, Shimizu T, Endo Y, Hanasawa K, Tani T (2006) Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis. J Surg Res 134:348–353

    Article  PubMed  CAS  Google Scholar 

  55. Marcheselli VL, Hong S, Lukiw WJ, Tian XH, Gronert K, Musto A, Hardy M, Gimenez JM, Chiang N, Serhan CN, Bazan NG (2003) Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. J Biol Chem 278:43807–43817

    Article  PubMed  CAS  Google Scholar 

  56. Serhan CN, Savill J (2005) Resolution of inflammation: the beginning programs the end. Nat Immunol 6:1191–1197

    Article  PubMed  CAS  Google Scholar 

  57. Walker A, Ward C, Taylor EL, Dransfield I, Hart SP, Haslett C, Rossi AG (2005) Regulation of neutrophil apoptosis and removal of apoptotic cells. Curr Drug Targets Inflamm Allergy 4:447–454

    Article  PubMed  CAS  Google Scholar 

  58. Fialkow L, Fochesatto Filho L, Bozzetti MC, Milani AR, Rodrigues Filho EM, Ladniuk RM, Pierozan P, de Moura RM, Prolla JC, Vachon E, Downey GP (2006) Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome. Crit Care 10:R155

    Article  PubMed  Google Scholar 

  59. Ariel A, Serhan CN (2007) Resolvins and protectins in the termination program of acute inflammation. Trends Immunol 28:176–183

    Article  PubMed  CAS  Google Scholar 

  60. Serhan CN (2005) Novel omega—3-derived local mediators in anti-inflammation and resolution. Pharmacol Ther 105:7–21

    Article  PubMed  CAS  Google Scholar 

  61. Hong S, Gronert K, Devchand PR, Moussignac RL, Serhan CN (2003) Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation. J Biol Chem 278:14677–14687

    Article  PubMed  CAS  Google Scholar 

  62. Levy BD, Kohli P, Gotlinger K, Haworth O, Hong S, Kazani S, Israel E, Haley KJ, Serhan CN (2007) Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J Immunol 178:496–502

    PubMed  CAS  Google Scholar 

  63. Gonzalez-Periz A, Planaguma A, Gronert K, Miquel R, Lopez-Parra M, Titos E, Horrillo R, Ferre N, Deulofeu R, Arroyo V, Rodes J, Claria J (2006) Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: protectin D1 and 17S-hydroxy-DHA. FASEB J 20:2537–2539

    Article  PubMed  CAS  Google Scholar 

  64. Duffield JS, Hong S, Vaidya VS, Lu Y, Fredman G, Serhan CN, Bonventre JV (2006) Resolvin D series and protectin D1 mitigate acute kidney injury. J Immunol 177:5902–5911

    PubMed  CAS  Google Scholar 

  65. Serhan CN, Gotlinger K, Hong S, Lu Y, Siegelman J, Baer T, Yang R, Colgan SP, Petasis NA (2006) Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: assignments of dihydroxy-containing docosatrienes. J Immunol 176:1848–1859

    PubMed  CAS  Google Scholar 

  66. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN (2005) Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 174:4345–4355

    PubMed  CAS  Google Scholar 

  67. Schwab JM, Chiang N, Arita M, Serhan CN (2007) Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 447:869–874

    Article  PubMed  CAS  Google Scholar 

  68. Ariel A, Fredman G, Sun YP, Kantarci A, Van Dyke TE, Luster AD, Serhan CN (2006) Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression. Nat Immunol 7:1209–1216

    Article  PubMed  CAS  Google Scholar 

  69. Watkins LR, Maier SF (2005) Immune regulation of central nervous system functions: from sickness responses to pathological pain. J Intern Med 257:139–155

    Article  PubMed  CAS  Google Scholar 

  70. Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117:289–296

    Article  PubMed  CAS  Google Scholar 

  71. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  PubMed  CAS  Google Scholar 

  72. Altavilla D, Guarini S, Bitto A, Mioni C, Giuliani D, Bigiani A, Squadrito G, Minutoli L, Venuti FS, Messineo F, De Meo V, Bazzani C, Squadrito F (2006) Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects against splanchic artery occlusion shock. Shock 25:500–506

    Article  PubMed  CAS  Google Scholar 

  73. Guarini S, Altavilla D, Cainazzo MM, Giuliani D, Bigiani A, Marini H, Squadrito G, Minutoli L, Bertolini A, Marini R, Adamo EB, Venuti FS, Squadrito F (2003) Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock. Circulation 107:1189–1194

    Article  PubMed  Google Scholar 

  74. Mioni C, Bazzani C, Giuliani D, Altavilla D, Leone S, Ferrari A, Minutoli L, Bitto A, Marini H, Zaffe D, Botticelli AR, Iannone A, Tomasi A, Bigiani A, Bertolini A, Squadrito F, Guarini S (2005) Activation of an efferent cholinergic pathway produces strong protection against myocardial ischemia/reperfusion injury in rats. Crit Care Med 33:2621–2628

    Article  PubMed  CAS  Google Scholar 

  75. de Jonge WJ, van der Zanden EP, The FO, Bijlsma MF, van Westerloo DJ, Bennink RJ, Berthoud HR, Uematsu S, Akira S, van den Wijngaard RM, Boeckxstaens GE (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nat Immunol 6:844–851

    Article  PubMed  CAS  Google Scholar 

  76. Reed MJ, Robertson CE, Addison PS (2005) Heart rate variability measurements and the prediction of ventricular arrhythmias. QJM 98:87–95

    Article  PubMed  CAS  Google Scholar 

  77. Schmidt H, Muller-Werdan U, Hoffmann T, Francis DP, Piepoli MF, Rauchhaus M, Prondzinsky R, Loppnow H, Buerke M, Hoyer D, Werdan K (2005) Autonomic dysfunction predicts mortality in patients with multiple organ dysfunction syndrome of different age groups. Crit Care Med 33:1994–2002

    Article  PubMed  Google Scholar 

  78. Pavlov VA, Ochani M, Gallowitsch-Puerta M, Ochani K, Huston JM, Czura CJ, Al-Abed Y, Tracey KJ (2006) Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proc Natl Acad Sci USA 103:5219–5223

    Article  PubMed  CAS  Google Scholar 

  79. O’Keefe JH Jr, Abuissa H, Sastre A, Steinhaus DM, Harris WS (2006) Effects of omega-3 fatty acids on resting heart rate, heart rate recovery after exercise, and heart rate variability in men with healed myocardial infarctions and depressed ejection fractions. Am J Cardiol 97:1127–1130

    Article  PubMed  CAS  Google Scholar 

  80. Das UN (2000) Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fatty Acids 63:351–362

    Article  PubMed  CAS  Google Scholar 

  81. Pluess TT, Hayoz D, Berger MM, Tappy L, Revelly JP, Michaeli B, Carpentier YA, Chiolero RL (2007) Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects. Intensive Care Med 33:789–797

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Endocrinology, Diabetes Services, Rabin Medical Center, Beilinson Hospital, Petach Tikva, 49100, Israel

    Joelle Singer

  2. Department of General Intensive Care, Institute for Nutrition Research, Petach Tikva, Israel

    Pierre Singer, Haim Shapiro, Miryam Theilla, Ronit Anbar & Jonathan Cohen

  3. The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Pierre Singer, Haim Shapiro, Miryam Theilla, Ronit Anbar & Jonathan Cohen

Authors
  1. Pierre Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haim Shapiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miryam Theilla
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ronit Anbar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Joelle Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jonathan Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pierre Singer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Singer, P., Shapiro, H., Theilla, M. et al. Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensive Care Med 34, 1580–1592 (2008). https://doi.org/10.1007/s00134-008-1142-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00134-008-1142-4

Keywords

Search

Navigation