Background Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P<0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p<0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (Ptrend<0.001), n-6 LCPUFA (Ptrend = 0.001), and total LCPUFA (Ptrend<0.001) and decreased linearly with the proportions of total MUFA (Ptrend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.
References
[1]
Hjern A, Rasmussen F, Hedlin G (1999) Age at adoption, ethnicity and atopic disorder: a study of internationally adopted young men in Sweden. Pediatr Allergy Immunol 10: 101–106.
[2]
Strachan DP (1989) Hay fever, hygiene, and household size. BMJ 299: 1259–1260.
[3]
Wang M, Karlsson C, Olsson C, Adlerberth I, Wold AE, et al. (2008) Reduced diversity in the early fecal microbiota of infants with atopic eczema. J Allergy Clin Immunol 121: 129–134.
[4]
Dunder T, Kuikka L, Turtinen J, R？s？nen L, Uhari M (2001) Diet, serum fatty acids, and atopic diseases in childhood. Allergy 56: 425–428.
[5]
Sausenthaler S, Kompauer I, Borte M, Herbarth O, Schaaf B, et al. (2006) Margarine and butter consumption, eczema and allergic sensitization in children. The LISA birth cohort study. Pediatr Allergy Immunol 17: 85–93.
[6]
Bolte G, Winkler G, Holscher B, Thefeld W, Weiland SK, et al. (2005) Margarine consumption, asthma, and allergy in young adults: results of the German National Health Survey 1998. Ann Epidemiol 15: 207–213.
[7]
Calvani M, Alessandri C, Sopo SM, Panetta V, Pingitore G, et al. (2006) Consumption of fish, butter and margarine during pregnancy and development of allergic sensitizations in the offspring: role of maternal atopy. Pediatr Allergy Immunol 17: 94–102.
[8]
Brix S, Lund P, Kjaer T, Straarup E, Hellgren L, et al. (2009) CD4+ T-cell activation is differentially modulated by bacteria-primed dendritic cells, but is generally down-regulated by n-3 polyunsaturated fatty acids. Immunology 129: 338–350.
[9]
Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, et al. (1991) Oral (n-3) Fatty Acid Supplementation Suppresses Cytokine Production and Lymphocyte Proliferation: Comparison between Young and Older Women. J Nutr 121: 547–555.
[10]
Zurier RB, Rossetti RG, Seiler CM, Laposata M (1999) Human peripheral blood T lymphocyte proliferation after activation of the T cell receptor: effects of unsaturated fatty acids. Prostaglandins Leukot Essent Fatty Acids 60: 371–375.
[11]
Fritsche KL, Byrge M, Feng C (1999) Dietary omega-3 polyunsaturated fatty acids from fish oil reduce interleukin-12 and interferon-gamma production in mice. Immunol Lett 65: 167–173.
[12]
Wallace FA, Miles EA, Evans C, Stock TE, Yaqoob P, et al. (2001) Dietary fatty acids influence the production of Th1- but not Th2-type cytokines. J Leukoc Biol 69: 449–457.
[13]
Calder PC, Newsholme EA (1992) Polyunsaturated fatty acids suppress human peripheral blood lymphocyte proliferation and interleukin-2 production. Clin Sci 82: 695–700.
[14]
Santoli D, Phillips PD, Colt TL, Zurier RB (1990) Suppression of interleukin 2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Evidence for a PGE-independent mechanism of inhibition by the fatty acids. J Clin Invest 85: 424–432.
[15]
Calder PC, Bond JA, Bevan SJ, Hunt SV, Newsholme EA (1991) Effect of fatty acids on the proliferation of concanavalin A-stimulated rat lymph node lymphocytes. Int J Biochem 23: 579–588.
[16]
Weyman C, Belin J, Smith AD, Thompson RHS (1975) Linoleic acid as an immunosuppressive agent. Lancet 2: 33.
[17]
Purasiri P, McKechnie A, Heys SD, Eremin O (1997) Modulation in vitro of human natural cytotoxicity, lymphocyte proliferative response to mitogens and cytokine production by essential fatty acids. Immunology 92: 166–172.
[18]
Khalfoun B, Thibault G, Lacord M, Gruel Y, Bardos P, et al. (1996) Docosahexaenoic and eicosapentaenoic acids inhibit human lymphoproliferative responses in vitro but not the expression of T cell surface activation markers. Scand J Immunol 43: 248–256.
[19]
Cunningham P, McDermott L (2009) Long Chain PUFA Transport in Human Term Placenta. J Nutr 139: 636–639.
[20]
Sandin A, Bjorksten B, Braback L (2004) Development of atopy and wheezing symptoms in relation to heredity and early pet keeping in a Swedish birth cohort. Pediatr Allergy Immunol 15: 316–322.
[21]
International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee (1998) Phase II Modules of the International Study of Asthma and Allergies in Childhood (ISAAC). Munster.
[22]
Hanifin J, Rajka G (1980) Diagnostic features of atopic dermatitis. Acta Derm Venereol Suppl. 92: 44–47.
[23]
Lepage G, Roy CC (1984) Improved recovery of fatty acid through direct transesterification without prior extraction or purification. J Lipid Res 25: 1391–1396.
[24]
Lee CM, Trevino B, Chaiyawat M (1996) A simple and rapid solvent extraction method for determining total lipids in fish tissue. J AOAC Int 79: 487–492.
[25]
Kaluzny MA, Duncan LA, Merritt MV, Epps DE (1985) Rapid separation of lipid classes in high yield and purity using bonded phase columns. J Lipid Res 26: 135–140.
[26]
Spergel JM, Paller AS (2003) Atopic dermatitis and the atopic march. J Allergy Clin Immunol 112: S118–S127.
[27]
Kamp F, Guo W, Souto R, Pilch PF, Corkey BE, et al. (2003) Rapid Flip-flop of Oleic Acid across the Plasma Membrane of Adipocytes. J Biol Chem 278: 7988–7995.
Strachan D (1989) Hay fever, hygiene, and household size. Br Med J 299: 1259–1260.
[30]
Strachan D (2000) Family size, infection and atopy: the first decade of the “hygiene hypothesis”. Thorax 55: S2–10.
[31]
Williams HC, Strachan DP, Hay RJ (1994) Childhood eczema: disease of the advantaged? BMJ 308: 1132–1135.
[32]
Kramer U, Heinrich J, Wjst M, Wichmann HE (1999) Age of entry to day nursery and allergy in later childhood. Lancet 353: 450–454.
[33]
Riedler J, Braun-Fahrlander C, Eder W, Schreuer M, Waser M, et al. (2001) Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 358: 1129–1133.
[34]
Hesselmar B, ？berg N, ？berg B, Eriksson B, Bjorksten B (1999) Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 29: 611–617.
[35]
Martricardi P, Ronchetti R (2001) Are infections protecting from atopy? Curr Opin Allergy Clin Immunol 1: 413–419.
[36]
Pelosi U, Porcedda G, Tiddia F, Tripodi S, Tozzi AE, et al. (2005) The inverse association of salmonellosis in infancy with allergic rhinoconjunctivitis and asthma at school-age: a longitudinal study. Allergy 60: 626–630.
[37]
Ismail IH, Oppedisano F, Joseph SJ, Boyle RJ, Licciardi PV, et al. (2012) Reduced gut microbial diversity in early life is associated with later development of eczema but not atopy in high-risk infants. Pediatr Allergy Immunol 23: 674–681.
[38]
Hesselmar B, Sj？berg F, Saalman R, ？berg N, Adlerberth I, et al.. (2013) Pacifier cleaning practices and risk of allergy development. Pediatrics. In Press.
[39]
Albers R, Bol M, Willems A, Blonk C, Pieters R (2002) Effects of dietary lipids on immune function in a murine sensitisation model. Br J Nutr 88: 291–299.
[40]
Chang H-H, Chen C-S, Lin J-Y (2009) Dietary perilla oil lowers serum lipids and ovalbumin-specific IgG1, but increases total IgE levels in ovalbumin-challenged mice. Food Chem Toxicol 47: 848–854.
Zhang P, Smith R, Chapkin RS, McMurray DN (2005) Dietary (n-3) Polyunsaturated Fatty Acids Modulate Murine Th1/Th2 Balance toward the Th2 Pole by Suppression of Th1 Development. J Nutr 135: 1745–1751.
[43]
Holt PG, Rowe J, Loh R, Sly PD (2003) Developmental factors associated with risk for atopic disease: implications for vaccine strategies in early childhood. Vaccine 21: 3432–3435.
[44]
Gold DR, Willwerth BM, Tantisira KG, Finn PW, Schaub B, et al. (2006) Associations of cord blood fatty acids with lymphocyte proliferation, IL-13, and IFN-γ. J Allergy Clin Immunol 117: 931–938.
[45]
Galli C, Calder PC (2009) Effects of Fat and Fatty Acid Intake on Inflammatory and Immune Responses: A Critical Review. Ann Nutr Metab 55: 123–139.
[46]
Yaqoob P (2002) Monounsaturated fatty acids and immune function. Eur J Clin Nutr 56: S9–S13.
[47]
Byberg K, Oymar K, Aksnes L (2008) Fatty acids in cord blood plasma, the relation to soluble CD23 and subsequent atopy. Prostaglandins Leukot Essent Fatty Acids 78: 61–65.
[48]
Duchén K, Casas R, Fager？s B？ttcher M, Yu G, Bj？rkstén B (2000) Human milk polyunsaturated longchain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy. Pediatr Allergy Immunol 11: 29–39.
[49]
Yu G, Bjorksten B (1998) Serum levels of phospholipid fatty acids in mothers and their babies in relation to allergic disease. Eur J Pediatr 157: 298–303.
[50]
Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, et al. (2003) Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 112: 1178–1184.
[51]
Furuhjelm C, Warstedt K, Fager？s M, F？lth-Magnusson K, Larsson J, et al. (2011) Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation. Pediatr Allergy Immunol 22: 505–514.
[52]
Furuhjelm C, Warstedt K, Larsson J, Fredriksson M, Bottcher MF, et al. (2009) Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy. Acta Paediatr 98: 1461–1467.
[53]
Olsen SF, Osterdal ML, Salvig JD, Mortensen LM, Rytter D, et al. (2008) Fish oil intake compared with olive oil intake in late pregnancy and asthma in the offspring: 16 y of registry-based follow-up from a randomized controlled trial. Am J Clin Nutr 88: 167–175.
[54]
Palmer DJ, Sullivan T, Gold MS, Prescott SL, Heddle R, et al.. (2012) Effect of n-3 long chain polyunsaturated fatty acid supplementation in pregnancy on infants' allergies in first year of life: randomised controlled trial. BMJ 344.
[55]
Alm B, Aberg N, Erdes L, Mollborg P, Pettersson R, et al. (2009) Early introduction of fish decreases the risk of eczema in infants. Arch Dis Child 94: 11–15.
[56]
Hesselmar B, Saalman R, Rudin A, Adlerberth I, Wold A (2010) Early fish introduction is associated with less eczema, but not sensitization, in infants. Acta Paediatr 99: 1861–1867.
[57]
Kull I, Bergstr？m A, Lilja G, Pershagen G, Wickman M (2006) Fish consumption during the first year of life and development of allergic diseases during childhood. Allergy 61: 1009–1015.
[58]
Nafstad P, Nystad W, Magnus P, Jaakkola JJ (2003) Asthma and allergic rhinitis at 4 years of age in relation to fish consumption in infancy. J Asthma 40: 343–348.
[59]
Johansson S, Lonnqvist A, Ostman S, Sandberg AS, Wold AE (2010) Long-chain polyunsaturated fatty acids are consumed during allergic inflammation and affect T helper type 1 (Th1)- and Th2-mediated hypersensitivity differently. Clin Exp Immunol 160: 411–419.
[60]
Johansson S, Wold AE, Sandberg AS (2011) Low breast milk levels of long-chain n-3 fatty acids in allergic women, despite frequent fish intake. Clin Exp Allergy 41: 505–515.
[61]
Grewe M, Walther S, Gyufko K, Czech W, Schopf E, et al. (1995) Analysis of the cytokine pattern expressed in situ in inhalant allergen patch test reactions of atopic dermatitis patients. J Invest Dermatol 105: 407–410.
