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Metabolic factors affecting the inflammatory response of periparturient dairy cows†

Published online by Cambridge University Press:  29 June 2009

Lorraine M. Sordillo ,
G. A. Contreras  and
Stacey L. Aitken
Lorraine M. Sordillo*
Affiliation:
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
G. A. Contreras
Affiliation:
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
Stacey L. Aitken
Affiliation:
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA
*
*Corresponding author. E-mail: [email protected]
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Abstract

Dairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.

Keywords

inflammationinnate immunitylipid mediatoroxidative stressperiparturientcattle
Type
Review Article
Information
Animal Health Research Reviews , Volume 10 , Issue 1 , June 2009 , pp. 53 - 63
Copyright
Copyright © Cambridge University Press 2009

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Footnotes

†

This paper is based on a presentation by Dr Sordillo as the Distinguished Veterinary Immunologist at the 89th Annual Meeting of the Conference of Research Workers in Animal Diseases (CRWAD), Chicago, 7 December 2008.

References

Aitken, SL, Karcher, EL, Rezamand, P, Gandy, JC, VandeHaar, MJ, Capuco, AV and Sordillo, LM (2009). Evaluation of antioxidant and proinflammatory gene expression in bovine mammary tissue during the periparturient period. Journal of Dairy Science 92: 589–598.CrossRefGoogle ScholarPubMed
Anderson, DE and Muir, WW (2005). Pain management in cattle. Veterinary Clinics of North America: Food Animal Practice 21: 623–635.Google ScholarPubMed
Asehnoune, K, Strassheim, D, Mitra, S, Kim, JY and Abraham, E (2004). Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappaB. Journal of Immunology 172: 2522–2529.CrossRefGoogle Scholar
Azzi, A (2004). The role of alpha-tocopherol in preventing disease. European Journal of Nutrition 43 (suppl. 1): I/18–25.CrossRefGoogle ScholarPubMed
Bannerman, DD and Goldblum, SE (2003). Mechanisms of bacterial lipopolysaccharide-induced endothelial apoptosis. American Journal of Physiology 284: L899–L914.Google ScholarPubMed
Bell, AW (1995). Regulation of organic nutrient metabolism during transition from late pregnancy to early lactation. Journal of Animal Science 73: 2804–2819.CrossRefGoogle ScholarPubMed
Bell, AW, Burhans, WS and Overton, TR (2000). Protein nutrition in late pregnancy, maternal protein reserves and lactation performance in dairy cows. Proceedings of the Nutrition Society 59: 119–126.CrossRefGoogle ScholarPubMed
Bernabucci, U, Ronchi, B, Lacetera, N and Nardone, A (2005). Influence of body condition score on relationships between metabolic status and oxidative stress in periparturient dairy cows. Journal of Dairy Science 88: 2017–2026.CrossRefGoogle ScholarPubMed
Bolick, DT, Orr, AW, Whetzel, A, Srinivasan, S, Hatley, ME, Schwartz, MA and Hedrick, CC (2005). 12/15-lipoxygenase regulates intercellular adhesion molecule-1 expression and monocyte adhesion to endothelium through activation of RhoA and nuclear factor-kappaB. Arteriosclerosis and Thrombosis Vascular Biology 25: 2301–2307.CrossRefGoogle ScholarPubMed
Bolick, DT, Srinivasan, S, Whetzel, A, Fuller, LC and Hedrick, CC (2006). 12/15 lipoxygenase mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of RhoA and NF-kappaB. Arteriosclerosis and Thrombosis Vascular Biology 26: 1260–1266.CrossRefGoogle ScholarPubMed
Bonomini, F, Tengattini, S, Fabiano, A, Bianchi, R and Rezzani, R (2008). Atherosclerosis and oxidative stress. Histology and Histopathology 23: 381–390.Google ScholarPubMed
Burvenich, C, Bannerman, DD, Lippolis, JD, Peelman, L, Nonnecke, BJ, Kehrli, ME Jr and Paape, MJ (2007). Cumulative physiological events influence the inflammatory response of the bovine udder to Escherichia coli infections during the transition period. Journal of Dairy Science 90 (suppl. 1): E39–E54.CrossRefGoogle ScholarPubMed
Calder, PC (2006). Polyunsaturated fatty acids and inflammation. Prostaglandins, Leukotrienes and Essential Fatty Acids 75: 197–202.CrossRefGoogle ScholarPubMed
Calder, PC (2008). The relationship between the fatty acid composition of immune cells and their function. Prostaglandins, Leukotrienes and Essential Fatty Acids 79: 101–108.CrossRefGoogle ScholarPubMed
Cao, YZ, Reddy, CC and Sordillo, LM (2000). Altered eicosanoid biosynthesis in selenium-deficient endothelial cells. Free Radicals in Biology and Medicine 28: 381–389.CrossRefGoogle ScholarPubMed
Cao, YZ, Cohen, ZS, Weaver, JA and Sordillo, LM (2001). Selenium modulates 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) biosynthesis in bovine aortic endothelial cells. Antioxidants and Redox Signaling 3: 1147–1152.CrossRefGoogle ScholarPubMed
Castillo, C, Hernandez, J, Valverde, I, Pereira, V, Sotillo, J, Alonso, ML and Benedito, JL (2006). Plasma malonaldehyde (MDA) and total antioxidant status (TAS) during lactation in dairy cows. Research in Veterinary Science 80: 133–139.CrossRefGoogle ScholarPubMed
Cebra, CK, Heidel, JR, Crisman, RO and Stang, BV (2003). The relationship between endogenous cortisol, blood micronutrients, and neutrophil function in postparturient Holstein cows. Journal of Veterinary Internal Medicine 17: 902–907.CrossRefGoogle ScholarPubMed
Chaiyotwittayakun, A, Erskine, RJ, Bartlett, PC, Herd, TH, Sears, PM and Harmont, RJ (2002). The effect of ascorbic acid and L-histidine therapy on acute mammary inflammation in dairy cattle. Journal of Dairy Science 85: 60–67.CrossRefGoogle Scholar
Christiaens, I, Zaragoza, DB, Guilbert, L, Robertson, SA, Mitchell, BF and Olson, DM (2008). Inflammatory processes in preterm and term parturition. Journal of Reproductive Immunology 79: 50–57.CrossRefGoogle ScholarPubMed
Corl, CM, Gandy, JC and Sordillo, LM (2008). Platelet activating factor production and proinflammatory gene expression in endotoxin-challenged bovine mammary endothelial cells. Journal of Dairy Science 91: 3067–3078.CrossRefGoogle ScholarPubMed
Douglas, GN, Rehage, J, Beaulieu, AD, Bahaa, AO and Drackley, JK (2007). Prepartum nutrition alters fatty acid composition in plasma, adipose tissue, and liver lipids of periparturient dairy cows. Journal of Dairy Science 90: 2941–2959.CrossRefGoogle ScholarPubMed
Drackley, JK, Overton, TR and Douglas, GN (2001). Adaptations of glucose and long-chain fatty acid metabolism in liver of dairy cows during the periparturient period. Journal of Dairy Science 84: E100–E112.CrossRefGoogle Scholar
Erskine, RJ, Eberhart, RJ, Grasso, PJ and Scholz, RW (1989). Induction of Escherichia coli mastitis in cows fed selenium-deficient or selenium-supplemented diets. American Journal of Veterinary Research 50: 2093–2100.Google ScholarPubMed
Erskine, RJ, Wagner, S and DeGraves, FJ (2003). Mastitis therapy and pharmacology. Veterinary Clinics of North America Food Animal Practice 19: 109–138, vi.CrossRefGoogle ScholarPubMed
Gitto, E, Reiter, RJ, Karbownik, M, Tan, DX, Gitto, P, Barberi, S and Barberi, I (2002). Causes of oxidative stress in the pre- and perinatal period. Biology of the Neonate 81: 146–157.CrossRefGoogle ScholarPubMed
Goff, JP (2006). Major advances in our understanding of nutritional influences on bovine health. Journal of Dairy Science 89: 1292–1301.CrossRefGoogle ScholarPubMed
Harats, D, Shaish, A, George, J, Mulkins, M, Kurihara, H, Levkovitz, H and Sigal, E (2000). Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice. Arteriosclerosis and Thrombosis Vascular Biology 20: 2100–2105.CrossRefGoogle ScholarPubMed
Herdt, TH (2000). Ruminant adaptation to negative energy balance. Influences on the etiology of ketosis and fatty liver. Veterinary Clinics of North America Food Animal Practice 16: 215–230.CrossRefGoogle ScholarPubMed
Hill, AW (1981). Factors influencing the outcome of Escherichia coli mastitis in the dairy cow. Research in Veterinary Science 31: 107–112.CrossRefGoogle ScholarPubMed
Hodgkinson, AJ, Carpenter, EA, Smith, CS, Molan, PC and Prosser, CG (2007). Adhesion molecule expression in the bovine mammary gland. Veterinary Immunology and Immunopathology 115: 205–215.CrossRefGoogle ScholarPubMed
Hogan, JS, Smith, KL, Weiss, WP, Todhunter, DA and Schockey, WL (1990). Relationships among vitamin E, selenium, and bovine blood neutrophils. Journal of Dairy Science 73: 2372–2378.CrossRefGoogle ScholarPubMed
Hogan, JS, Weiss, WP, Todhunter, DA, Smith, KL and Schoenberger, PS (1992). Bovine neutrophil responses to parenteral vitamin E. Journal of Dairy Science 75: 399–405.CrossRefGoogle ScholarPubMed
Jafari, A, Emmanuel, DGV, Christopherson, RJ, Thompson, JR, Murdoch, GK, Woodward, J, Field, CJ and Ametaj, BN (2006). Parenteral administration of glutamine modulates acute phase response in postparturient dairy cows. Journal of Dairy Science 89: 4660–4668.CrossRefGoogle ScholarPubMed
Kliewer, SA, Sundseth, SS, Jones, SA, Brown, PJ, Wisely, GB, Koble, CS, Devchand, P, Wahli, W, Willson, TM, Lenhard, JM and Lehmann, M Jr (1997). Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences of the United States of America 94: 4318–4323.CrossRefGoogle ScholarPubMed
Kühn, H and O'Donnell, VB (2006). Inflammation and immune regulation by 12/15-lipoxygenases. Progress in Lipid Research 45: 334–356.CrossRefGoogle ScholarPubMed
Langenbach, R, Morham, SG, Tiano, HF, Loftin, CD, Ghanayem, BI, Chulada, PC, Mahler, JF, Lee, CA, Goulding, EH, Kluckman, KD, Kim, HS and Smithies, O (1995). Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 83: 483–492.CrossRefGoogle ScholarPubMed
Langenbach, R, Loftin, CD, Lee, C and Tiano, H (1999). Cyclooxygenase-deficient mice: a summary of their characteristics and susceptibilities to inflammation and carcinogenesis. Annals of New York Academy of Science 889: 52–61.CrossRefGoogle ScholarPubMed
LeBlanc, SJ, Herdt, TH, Seymour, WM, Duffield, TF and Leslie, KE (2004). Peripartum serum vitamin E, retinol, and beta-carotene in dairy cattle and their associations with disease. Journal of Dairy Science 87: 609–619.CrossRefGoogle ScholarPubMed
Lee, JY, Sohn, KH, Rhee, SH and Hwang, D (2001). Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. Journal of Biological Chemistry 276: 16683–16689.CrossRefGoogle ScholarPubMed
Lee, JY, Plakidas, A, Lee, WH, Heikkinen, A, Chanmugam, P, Bray, G and Hwang, DH (2003). Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n−3 polyunsaturated fatty acids. Journal of Lipid Research 44: 479–486.CrossRefGoogle Scholar
Leroy, JL, Vanholder, T, Van Knegsel, AT, Garcia-Ispierto, I and Bols, PE (2008). Nutrient prioritization in dairy cows early postpartum: mismatch between metabolism and fertility? Reproduction in Domestic Animals 43: 96–103.CrossRefGoogle ScholarPubMed
Lippolis, JD (2008). Immunological signaling networks: integrating the body's immune response. Journal of Animal Science 86: E53–E63.CrossRefGoogle ScholarPubMed
Maddox, JF, Aherne, KM, Reddy, CC and Sordillo, LM (1999). Increased neutrophil adherence and adhesion molecule mRNA expression in endothelial cells during selenium deficiency. Journal of Leukocyte Biology 65: 658–664.CrossRefGoogle ScholarPubMed
Martins de lima, T, Gorjo, R, Hatanaka, E, Cury-boaventura, MF, Portiolisilva, EP, Procopio, J and Curi, R (2007). Mechanisms by which fatty acids regulate leucocyte function. Clinical Science 113: 65–77.CrossRefGoogle ScholarPubMed
Massaro, M, Scoditti, E, Carluccio, MA and De Caterina, R (2008). Basic mechanisms behind the effects of n−3 fatty acids on cardiovascular disease. Prostaglandins, Leukotrienes and Essential Fatty Acids 79: 109–115.CrossRefGoogle ScholarPubMed
Michal, JJ, Heirman, LR, Wong, TS, Chew, BP, Frigg, M and Volker, L (1994). Modulatory effects of dietary beta-carotene on blood and mammary leukocyte function in periparturient dairy cows. Journal of Dairy Science 77: 1408–1421.CrossRefGoogle ScholarPubMed
Miller, JK, Brzezinska-Slebodzinska, E and Madsen, FC (1993). Oxidative stress, antioxidants, and animal function. Journal of Dairy Science 76: 2812–2823.CrossRefGoogle ScholarPubMed
Morham, SG, Langenbach, R, Loftin, CD, Tiano, HF, Vouloumanos, N, Jennette, JC, Mahler, JF, Kluckman, KD, Ledford, A, Lee, CA and Smithies, O (1995). Prostaglandin synthase 2 gene disruption causes severe renal pathology in the mouse. Cell 83: 473–482.CrossRefGoogle ScholarPubMed
O'Boyle, N, Corl, CM, Gandy, JC and Sordillo, LM (2006). Relationship of body condition score and oxidant stress to tumor necrosis factor expression in dairy cattle. Veterinary Immunology and Immunopathology 113: 297–304.CrossRefGoogle ScholarPubMed
Otto, SJ, van Houwelingen, AC, Badart-Smook, A and Hornstra, G (2001). Comparison of the peripartum and postpartum phospholipid polyunsaturated fatty acid profiles of lactating and nonlactating women. American Journal of Clinical Nutrition 73: 1074–1079.CrossRefGoogle ScholarPubMed
Oviedo-Boyso, J, Valdez-Alarcon, JJ, Cajero-Juarez, M, Ochoa-Zarzosa, A, Lopez-Meza, JE, Bravo-Patino, A and Baizabal-Aguirre, VM (2007). Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis. Journal of Infection 54: 399–409.CrossRefGoogle ScholarPubMed
Politis, I, Hidiroglou, N, White, JH, Gilmore, JA, Williams, SN, Scherf, H and Frigg, M (1996). Effects of vitamin E on mammary and blood leukocyte function, with emphasis on chemotaxis, in periparturient dairy cows. American Journal of Veterinary Research 57: 468–471.CrossRefGoogle ScholarPubMed
Politis, I, Bizelis, I, Tsiaras, A and Baldi, A (2004). Effect of vitamin E supplementation on neutrophil function, milk composition and plasmin activity in dairy cows in a commercial herd. Journal of Dairy Research 71: 273–278.CrossRefGoogle Scholar
Prasad, R, Giri, S, Singh, AK and Singh, I (2008). 15-deoxy-delta12,14-prostaglandin J2 attenuates endothelial-monocyte interaction: implication for inflammatory diseases. Journal of Inflammation (London) 5: 14.CrossRefGoogle ScholarPubMed
Rainard, P and Riollet, C (2006). Innate immunity of the bovine mammary gland. Veterinary Research 37: 369–400.CrossRefGoogle ScholarPubMed
Rainsford, KD (2007). Anti-inflammatory drugs in the 21st century. Subcellular Biochemistry 42: 3–27.CrossRefGoogle ScholarPubMed
Rajakariar, R, Yaqoob, MM and Gilroy, DW (2006). COX-2 in inflammation and resolution. Molecular Interventions 6: 199–207.CrossRefGoogle ScholarPubMed
Rajakariar, R, Hilliard, M, Lawrence, T, Trivedi, S, Colville-Nash, P, Bellingan, G, Fitzgerald, D, Yaqoob, MM and Gilroy, DW (2007). Hematopoietic prostaglandin D2 synthase controls the onset and resolution of acute inflammation through PGD2 and 15-deoxyDelta12 14 PGJ2. Proceedings of the National Academy of Science of the United States of America 104: 20979–20984.CrossRefGoogle ScholarPubMed
Reilly, KB, Srinivasan, S, Hatley, ME, Patricia, MK, Lannigan, J, Bolick, DT, Vandenhoff, G, Pei, H, Natarajan, R, Nadler, JL and Hedrick, CC (2004). 12/15-Lipoxygenase activity mediates inflammatory monocyte/endothelial interactions and atherosclerosis in vivo. Journal of Biological Chemistry 279: 9440–9450.CrossRefGoogle ScholarPubMed
Serhan, CN, Chiang, N and Van Dyke, TE (2008). Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Review in Immunology 8: 349–361.CrossRefGoogle ScholarPubMed
Shi, H, Kokoeva, MV, Inouye, K, Tzameli, I, Yin, H and Flier, JS (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigations 116: 3015–3025.CrossRefGoogle ScholarPubMed
Shuster, DE, Kehrli, ME and Stevens, MG (1993). Cytokine production during endotoxin-induced mastitis in lactating dairy cows. American Journal of Veterinary Research 54: 80–85.CrossRefGoogle ScholarPubMed
Silva, E, Gaivão, M, Leitão, S, Amaro, A, Lopes da Costa, L and Mateus, L (2008). Blood COX-2 and PGES gene transcription during the peripartum period of dairy cows with normal puerperium or with uterine infection. Domestic Animal Endocrinology 35: 314–323.CrossRefGoogle ScholarPubMed
Smith, KL, Harrison, JH, Hancock, DD, Todhunter, DA and Conrad, HR (1984). Effect of vitamin E and selenium supplementation on incidence of clinical mastitis and duration of clinical symptoms. Journal of Dairy Science 67: 1293–1300.CrossRefGoogle ScholarPubMed
Sordillo, LM (2005). Factors affecting mammary gland immunity and mastitis susceptibility. Livestock Production Science 98: 89–99.CrossRefGoogle Scholar
Sordillo, LM and Aitken, SL (2009). Impact of oxidative stress on the health and immune function of dairy cattle. Veterinary Immunology and Immunopathology 128: 104–109.CrossRefGoogle ScholarPubMed
Sordillo, LM and Peel, JE (1992). Effect of interferon-gamma on the production of tumor necrosis factor during acute Escherichia coli mastitis. Journal of Dairy Science 75: 2119–2125.CrossRefGoogle ScholarPubMed
Sordillo, LM, Pighetti, GM and Davis, MR (1995). Enhanced production of bovine tumor necrosis factor-alpha during the periparturient period. Veterinary Immunology and Immunopathology 49: 263–270.CrossRefGoogle ScholarPubMed
Sordillo, LM, Weaver, JA, Cao, Y-Z, Corl, C, Sylte, MJ and Mullarky, IK (2005). Enhanced 15-HPETE production during oxidant stress induces apoptosis of endothelial cells. Prostaglandins and Other Lipid Mediators 76: 19–34.CrossRefGoogle ScholarPubMed
Sordillo, LM, O'Boyle, N, Gandy, JC, Corl, CM and Hamilton, E (2007). Shifts in thioredoxin reductase activity and oxidant status in mononuclear cells obtained from transition dairy cattle. Journal of Dairy Science 90: 1186–1192.CrossRefGoogle ScholarPubMed
Sordillo, LM, Streicher, KL, Mullarky, IK, Gandy, JC, Trigona, W and Corl, CM (2008). Selenium inhibits 15-hydroperoxyoctadecadienoic acid-induced intracellular adhesion molecule expression in aortic endothelial cells. Free Radicals in Biology and Medicine 44: 34–43.CrossRefGoogle ScholarPubMed
Spears, JW and Weiss, WP (2008). Role of antioxidants and trace elements in health and immunity of transition dairy cows. Veterinary Journal 176: 70–76.CrossRefGoogle ScholarPubMed
Stabel, JR, Reinhardt, TA, Stevens, MA, Kehrli, ME Jr and Nonnecke, BJ (1992). Vitamin E effects on in vitro immunoglobulin M and interleukin-1 beta production and transcription in dairy cattle. Journal of Dairy Science 75: 2190–2198.CrossRefGoogle ScholarPubMed
Valko, M, Leibfritz, D, Moncol, J, Cronin, MT, Mazur, M and Telser, J (2007). Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology 39: 44–84.CrossRefGoogle ScholarPubMed
Weaver, JA, Maddox, JF, Cao, YZ, Mullarky, IK and Sordillo, LM (2001). Increased 15-HPETE production decreases prostacyclin synthase activity during oxidant stress in aortic endothelial cells. Free Radical Biology and Medicine 30: 299–308.CrossRefGoogle ScholarPubMed
Weiss, WP and Hogan, JS (2007). Effects of dietary vitamin C on neutrophil function and responses to intramammary infusion of lipopolysaccharide in periparturient dairy cows. Journal of Dairy Science 90: 731–739.CrossRefGoogle ScholarPubMed
Weiss, WP, Hogan, JS, Smith, KL and Hoblet, KH (1990). Relationships among selenium, vitamin E, and mammary gland health in commercial dairy herds. Journal of Dairy Science 73: 381–390.CrossRefGoogle ScholarPubMed
Weiss, WP, Hogan, JS and Smith, KL (2004). Changes in vitamin C concentrations in plasma and milk from dairy cows after an intramammary infusion of Escherichia coli. Journal of Dairy Science 87: 32–37.CrossRefGoogle ScholarPubMed
Wood, LG, Scott, HA, Garg, ML and Gibson, PG (2009). Innate immune mechanisms linking non-esterified fatty acids and respiratory disease. Progress in Lipid Research 48: 27–43.CrossRefGoogle ScholarPubMed
Yaqoob, P and Calder, PC (2007). Fatty acids and immune function: new insights into mechanisms. British Journal of Nutrition 98: S41–S45.CrossRefGoogle ScholarPubMed