Skip to main content
SpringerLink
Log in

Long-chain polyunsaturated fatty acids and eicosanoids in infants-physiological and pathophysiological aspects and open questions

  • Published:
Lipids

Abstract

Eicosanoids are highly active lipid mediators in physiologic and pathologic processes, with their effects ranging from cytoprotection and vasoactivity to modulation of inflammatory and proliferative reactions. Generation of eicosanoids can be affected by changes in the pools of their precursors, the long-chain polyunsaturated fatty acids (LCPUFA). Thus, dietary interventions such as supplementation of infant formula with specific n−3 and n−6 LCPUFA will alter formation as well as activity of the eicosanoids produced. This report summarizes the results and discussion of the workshop on “Eicosanoids and Polyunsaturated Fatty Acids in Infants”. The intention of the workshop organizers was to give an overview of the role of eicosanoids in physiological and pathophysiological processes in infants, to discuss the implications that an increased n−3 and n−6 LCPUFA intake may have on eicosanoid genration, and to point out open questions and controversies for future research.

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

Similar content being viewed by others

Abbreviations

CNS:

central nervous system

HETE:

hydroxyeicosatetraenoic acid

LCPUFA:

long chain polyunsaturated fatty acid

LT:

leukotriene

PG:

prostaglandin

Tx:

thromboxane

References

  1. Hershman, H.R. (1996) Prostaglandin Synthase 2, Biochim. Biophys. Acta 1299, 125–140.

    Google Scholar 

  2. Henderson, R.H. (1994) The Role of Leukotrienes in Inflammation, Ann. Int. Med. 121, 684–697.

    PubMed  CAS  Google Scholar 

  3. McGiff, J.C. (1991) Cytochrome P450 Metabolism of Arachidonic Acid, Annu. Rev. Pharmacol. Toxicol. 31, 339–369.

    Article  PubMed  CAS  Google Scholar 

  4. Clària, J., and Serhan, C.N. (1995) Asprin Triggers Previously Undescribed Bioactive Eicosanoids by Human Endothelial Cell-Leukocyte Interactions, Proc. Natl. Acad. Sci. USA 92, 9475–9479.

    Article  PubMed  Google Scholar 

  5. Stenke, L., Reizenstein, P., and Lindgren, Å. (1994) Leukotrienes and Lipoxins—New Potential Performers In the Regulation of Human Myelopoiesis, Leukemia Res. 18, 727–732.

    Article  CAS  Google Scholar 

  6. Khan, W.A., Blobe, G.C., and Hannun, Y.A. (1995) Arachidonic Acid and Free Fatty Acids as Second Messengers and the Role of Protein Kinase C, Cell. Signal 7, 171–184.

    Article  PubMed  CAS  Google Scholar 

  7. Leaf, A., and Weber, P.C. (1988) Cardiovascular Effects of n−3 Fatty Acids, N. Engl. J. Med. 318, 549–557.

    Article  PubMed  CAS  Google Scholar 

  8. Weber, P.C., Fischer, S., von Schacky, C., Lorenz, R., and Strasser, T. (1986) The Conversion of Dietary Eicosapentaenoic Acid to Prostanoids and Leukotrienes in Man, Prog. Lipid Res. 25, 273–276.

    Article  PubMed  CAS  Google Scholar 

  9. Knapp, H.R. (1995) Omega-3 Fatty Acids in Respiratory Diseases: A Review, J. Am. Coll. Nutr. 14, 18–23.

    PubMed  CAS  Google Scholar 

  10. Seyberth, H.W., Knapp, G., Wolf, D., and Ulmer, H.E. (1983) Introduction of Plasma Indomethacin Level Monitoring and Evaluation of an Effective Threshold Level in Very Low Birthweight Infants with Symptomatic Patent Ductus Arteriosus, Eur. J. Pediatr. 141, 71–76.

    Article  PubMed  CAS  Google Scholar 

  11. Leonhardt, A., Busch, C., Schweer, H., and Seyberth, H.W. (1992) Reference Intervals and Developmental Changes in Urinary Prostanoid Excretion in Healthy Newborns, Infants and Children, Acta Paediatr. Scand. 81, 191–196.

    CAS  Google Scholar 

  12. Uauy, R., Hoffmann, D.R., Birch, E.E., Birch, D.G., Jameson, D.M., and Tyson, J. (1994) Safety and Efficacy of Omega-3 Fatty Acids in the Nutrition of Very Low Birth Weight Infants: Soy Oil and Marine Oil Supplementation of Formula, J. Pediatr. 124, 612–620

    Article  PubMed  CAS  Google Scholar 

  13. Juzan, M., Hostein, I., and Gualde, N. (1992) Role of Thymus-Eicosanoids in the Immune Response, Prostaglandins Leukotrienes Essent. Fatty Acids 46, 247–255.

    Article  CAS  Google Scholar 

  14. Roper, R.L., and Phipps, R.P. (1992) Prostaglandin E2 and cAMP Inhibit B Lymphocyte Activation and Simultaneously Promote IgE and IgG1 Synthesis, J. Immunol. 149, 2984–2991.

    PubMed  CAS  Google Scholar 

  15. Goetzl, E.J., Songhzu, A., and Smith, W.L. (1995) Specificity of Expression and Effects of Eicosanoid Mediators in Normal Physiology and Human Diseases, FASEB J. 9, 1051–1058.

    PubMed  CAS  Google Scholar 

  16. Claesson, H.-E., Odlander, B., and Jakobsson, P.-J. (1992) Leukotriene B4 in the Immune Systems, Int. J. Immunopharmacol. 14, 441–449.

    Article  PubMed  CAS  Google Scholar 

  17. Knapp, H.R. (1990) Prostaglandins in Human Semen During Fish Oil Ingestion: Evidence for in vivo Cyclooxygenase Inhibition and Appearance of Novel Trienoic Compounds, Prostaglandins 39, 407–423.

    Article  PubMed  CAS  Google Scholar 

  18. Lawrence, R., and Sorrell, T. (1993) Eicosapentaenoic Acid in Cystic Fibrosis: Evidence of a Pathogenetic Role for Leukotriene B4, Lancet 342, 465–469.

    Article  PubMed  CAS  Google Scholar 

  19. Lawrence, R.H., and Sorrell, T.C. (1994) Eicosapentaenoic Acid Modulates Neutrophil Leukotriene B4 Receptor Expression in Cystic Fibrosis, Clin. Exp. Immunol. 98, 12–16.

    Article  PubMed  CAS  Google Scholar 

  20. Kremer, J.M. (1991) Clinical Studies of Omega-3 Fatty Acid Supplementation in Patients Who Have Rheumatoid Arthritis, Rheum. Dis. Clin. North Am. 17, 391–402.

    PubMed  CAS  Google Scholar 

  21. Donadio, J.V., Bergstrahl, E.J., Offord, K.P., Spencer, D.C., Holley, K.E., and the M.N.C. Group (1994) A Controlled Trial of Fish Oil In IgA Nephropathy, N. Engl. J. Med. 331, 1194–1199.

    Article  PubMed  Google Scholar 

  22. Homan van der Heide, J.J., Bilo, H.J.G., Donker, J.M., Wilmink, J.J., and Tegzess, A.M. (1993) Effect of Dietary Fish Oil on Renal Function and Rejection in Cyclosporine-Treated Recipients of Renal Transplants, N. Engl. J. Med. 329, 769–773.

    Article  Google Scholar 

  23. Kooijmans-Coutinho, M.F., Rischen-Vos, J., Hermans, J., Arndt, J.-W., and van der Woude, F.J. (1996) Dietary Fish Oil in Renal Transplant Recipients Treated with Cyclosporin-A: No Beneficial Effects Shown, J. Am. Soc. Nephrol. 7, 513–518.

    PubMed  CAS  Google Scholar 

  24. Clark, W.F., and Parbtani, A. (1994) Omega-3 Fatty Acid Supplementation in Clinical and Experimental Lupus Nephritis, Am. J. Kidney Dis. 23, 644–647.

    PubMed  CAS  Google Scholar 

  25. Robinson, D.R., Prickett, J.D., Makoul, G.T., Steinberg, A.D., and Calvin, R.B. (1986) Dietary Fish Oil Reduces Progression of Established Renal Disease in (NZB×NZW)F1 Mice and Delays Renal Disease in BXSB and MRL/I Strains, Arthritis Rheum. 29, 539–546.

    PubMed  CAS  Google Scholar 

  26. Fernandes, G., Bysani, C., Venkatraman, J.T., Tomar, V., and Zhao, W. (1994) Increased TGF-β and Decreased Oncogene Expression by ω-3 Fatty Acids in the Spleen Delays Onset of Autoimmune Disease in B/W Mice, J. Immunol. 152, 5979–5987.

    PubMed  CAS  Google Scholar 

  27. Meydani, S.N. (1992) Modulation of Cytokine Production by Dietary Polyunsaturated Fatty Acids, Proc. Soc. Exp. Biol. Med. 200, 189–193.

    PubMed  CAS  Google Scholar 

  28. Caygill, C.P.J., Charlett, A., and Hill, M.J. (1996) Fat, Fish Oil and Cancer, Br. J. Cancer 74, 159–164.

    PubMed  CAS  Google Scholar 

  29. Sassen, L.M.A., Lamers, J.M.J., and Verdouw, P.D. (1994) Fish Oil and the Prevention and Regression of Atherosclerosis, Cardiovascs. Drugs Therapy 8, 179–191.

    Article  CAS  Google Scholar 

  30. Olsen, S.F., Sørensen, J.D., Secher, N.J., Hedegaard, M., henriksen, T.B., Hansen, H.S., and Grant, A. (1992) Randomised Controlled Trial of Effect of Fish-Oil Supplementation on Pregnancy Duration, Lancet 339, 1003–1007.

    Article  PubMed  CAS  Google Scholar 

  31. Innis, S.M., Akrabawi, S.S., Diersen-Schade, D.A., Dobson, M.V., and Guy, D.G. (1997) Visual Acuity and Blood Lipids in Term Infants Fed Human Milk or Formulae, Lipids 32, 63–72.

    Article  PubMed  CAS  Google Scholar 

  32. Auestad, N., Montalto, M.B., Hall, R.T., Fitzgerald, K.M., Wheeler, R.E., Connor, W.E., Neuringer, M., Connor, S.L., Taylor, J.A., and Hartmann, E.F. (1997) Visual Acuity, Erythrocyte Fatty Acid Composition, and Growth in Term Infants Fed Formulas with Long Chain Polyunsaturated Fatty Acids for One Year. Ross Pediatric Lipid Study, Pediatr. Res. 41, 1–10.

    PubMed  CAS  Google Scholar 

  33. Jensen, C.L., Prager, T.C., Fraley, J.K., Chen, H., Anderson, R.E., and Heird, W.C. (1997) Effect of Dietary Linoleic/alpha-Linolenic Acid Ratio on Growth and Visual Function of Term Infants, J. Pediatr. 131, 200–209.

    Article  PubMed  CAS  Google Scholar 

  34. Carlson, S.E., Cooke, R.J., Werkman, S.H., and Tolley, E.A., (1992) First Year Growth in Preterm Infants Fed Standard Compared to Marine Oil n−3 Supplemented Formula, Lipids 27, 901–907.

    PubMed  CAS  Google Scholar 

  35. Carlson, S.E. (1996) Arachidonic Acid Status of Human Infants: Influence of Gestational Age at Birth and Diets with Very Long Chain n−3 and n−6 Fatty Acids, J. Nutr. 126 (4 Suppl.), 1092S-1098S.

    PubMed  CAS  Google Scholar 

  36. Koletzko, B., and Braun, M. (1991) Arachidonic Acid and Early Human Growth: Is There a Relation?, Ann. Nutr. Metab. 35, 128–131.

    Article  PubMed  CAS  Google Scholar 

  37. Carlson, S.E., Werkman, M.J., and Tolley, E.A. (1996) Effect of Long-Chain n−3 Fatty Acid Supplementation on Visual Acuity and Growth in Pretern Infants with and Without Bronchopulmonary Dysplasia, Am. J. Clin. Nutr. 63, 687–697.

    PubMed  CAS  Google Scholar 

  38. Leaf, A.A., Leighfield, M.J., Costeloe, K.L., and Crawford, M.A. (1992) Long Chain Polyunsaturated Fatty Acids and Fetal Growth, Early Hum. Dev. 30, 183–191.

    Article  PubMed  CAS  Google Scholar 

  39. Sellmayer, A., Uedelhoven, W.M., Weber, P.C., and Bonventre, J.V. (1991) Endogenous Non-cyclooxygenase Metabolites of Arachidonic Acid Modulate Growth and mRNA Levels of Immediate-Early Response Genes in Rat Mesangial Cells, J. Biol. Chem. 266, 3800–3807.

    PubMed  CAS  Google Scholar 

  40. Handler, J.A., Danilowicz, R.M., and Eling, T.E. (1990) Mitogenic Signaling by Epidermal Growth Factor (EGF), but Not Platelet-Derived Growth Factor, Requires Arachidonic Acid Metabolism In BALB/c 3T3 Cells, J. Biol. Chem. 265, 3669–3673.

    PubMed  CAS  Google Scholar 

  41. Lupulescu, A. (1996) Prostaglandins, Their Inhibitors and Cancer, Prostaglandins Leukotrienes Essent. Fatty Acids. 54, 83–94.

    Article  CAS  Google Scholar 

  42. Danesch, U., Weber, P.C., and Sellmayer, A. (1996) Differential Effects of n−6 and n−3 Polyunsaturated Fatty Acids on Cell Growth and Early Gene Expression in Swiss 3T3 Fibroblasts, J. Cell. Physiol. 168, 618–624.

    Article  PubMed  CAS  Google Scholar 

  43. Scales, W.E., and Kluger, M.J. (1987) Effect of Antipyretic Drugs on Circadian Rhythm in Body Temperature of Rats, Am. J. Physiol. 253, R306-R313.

    PubMed  CAS  Google Scholar 

  44. Davis, G.W., and Murphey, R.K. (1994) Long-Term Regulation of Short-Term Transmitter Release Properties: Retrograde Signalling and Synaptic Development, Trends Neurosci. 17, 9–13.

    Article  PubMed  CAS  Google Scholar 

  45. Horrobin, D.F., and Manku, M.S. (1980) Possible Role of Prostaglandin E1 in the Affective Disorders and in Alcoholism, Br. Med. J. 280, 1361–1366.

    Article  Google Scholar 

  46. Onoe, H., Ueno, R., Fuita, I., Nishino, H., Oomura, Y., and Hayaishi, O. (1988) Prostaglandin D2, a Cerebral Sleep-Inducting Substance in Monkeys, Proc. Natl. Acad. Sci. USA 85, 4082–4086.

    Article  PubMed  CAS  Google Scholar 

  47. Srikantha, S., Matsumura, H., Kubo, E., Kawase, K., Takahata, R., Serhan, C.N., and Hayaishi, O. (1994) Effects of Prostaglandin D2, Lipoxins and Leukotrienes on Sleep and Brain Temperature of Rats, Prostaglandins Leukotrienes Essent. Fatty Acids 51, 87–93.

    Article  CAS  Google Scholar 

  48. Matsumura, H., Honda, K., Goh, Y., Ueno, R., Sakai, T., Inoue, S., and Hayaishi, O. (1989) Awaking Effect of Prostaglandin E2 in Freely Moving Rats, Brain Res. 481, 242–249.

    Article  PubMed  CAS  Google Scholar 

  49. Fagioli, L., Baroncini, P., Ricour, C., and Salzarulo, P. (1989) Decrease of Slow-Wave Sleep in Children with Prolonged Absence of Essential Lipids Intake, Sleep 12, 495–499.

    PubMed  CAS  Google Scholar 

  50. Huang, M.-C., and Craig-Schmidt, M.C. (1996) Arachidonate and Docosahexaenoate Added to Infant Formula Influence Fatty Acid Composition and Subsequent Eicosanoid Production in Neonatal Pigs, J. Nutr. 126, 2199–2208.

    PubMed  CAS  Google Scholar 

  51. Griswold, D.E., and Adams, J.L. (1996) Constitutive Cyclooxygenase (COX-1) and Inducible Cyclooxygenase (COX-2): Rationale for Selective Inhibition and Progress to Date, Medicin. Res. Rev. 16, 181–206.

    Article  CAS  Google Scholar 

  52. Mayatepek, E., and Hoffmann, G.F. (1995) Leukotrienes: Biosynthesis, Metabolism and Pathophysiologic Significance, Ped. Res. 37, 1–9.

    CAS  Google Scholar 

  53. Thien, F.C.K., and Walters, E.H. (1995) Eicosanoids and Asthma, Prostaglandins Leukotrienes Essent. Fatty Acids 52, 271–288.

    Article  CAS  Google Scholar 

  54. Israels, S.J., Odaibo, F.S., Robertson, C., McMillan, E.M., and McNicol, A. (1997) Defrelent Thromboxane Synthesis and Response in Platelets from Premature Infants, Pediatr. Res. 41, 218–223.

    PubMed  CAS  Google Scholar 

  55. Cheromcha, D.P., and Hyman, P.E. (1988) Neonatal Necrotizing Enterocolitis. Inflammatory Bowel Disease of the Newborn, Dig. Dis. Sci. 33, (3 Suppl.), 78S-84S.

    Article  PubMed  CAS  Google Scholar 

  56. Stenmark, K.R., James, S.L., Voelkel, N.F., Toews, W.H., Reeves, J.T., and Murphy, R.C. (1983) Leukotrienes C4 and D4 in Neonates with Hypoxemia and Pulmonary Hypertension, N. Engl. J. Med. 309, 77–80.

    Article  PubMed  CAS  Google Scholar 

  57. Groneck, P., Gotze-Speer, B., Oppermann, M., Eiffert, H., and Speer, C.P. (1994) Association of Pulmonary Inflammation and Increased Microvascular Permeability During the Development of Bronchopulmonary Dysplasia: A Sequential Analysis of Inflammatory Mediators in Respiratory Fluids of High-Risk Preterm Neonates, Pediatrics. 93, 712–718.

    PubMed  CAS  Google Scholar 

  58. Watterberg, K.L., Demers, L.M., Scott, S.M., and Murphy, S. (1996) Chorloamnionitis and Early Lung Inflammation in Infants in Whom Bronchopulmonary Dysplasia Develops, Pediatrics 97, 210–215.

    PubMed  CAS  Google Scholar 

  59. Guignard, J.P., Gouyon, J.B., and John, E.G. (1991) Vasoactive Factors in the Immature Kidney, Pediatr. Nephrol. 5, 443–446.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Metabolic Diseases and Nutrition, Dr. Von Haunersches Kinderspital, Klinikum Innenstadt, University of Munich, Germany

    Berthold Koletzko

  2. Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Pettenkoferstr. 9, 80336, München, Germany

    Alois Sellmayer

Authors
  1. Alois Sellmayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Berthold Koletzko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alois Sellmayer.

About this article

Cite this article

Sellmayer, A., Koletzko, B. Long-chain polyunsaturated fatty acids and eicosanoids in infants-physiological and pathophysiological aspects and open questions. Lipids 34, 199–205 (1999). https://doi.org/10.1007/s11745-999-0354-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-999-0354-z

Keywords

Search

Navigation