Low maternal dietary vitamin E (but not vitamin C) intake during pregnancy has been associated with increased in vitro cord blood mononuclear cell (CBMC) proliferative responses, childhood wheezing and asthma. We investigated whether these associations reflect direct effects of vitamin E by investigating the effects of supplementing CBMC cultures with physiological concentrations of vitamin E. CBMC from seventy neonates were cultured supplemented with either nothing, α-tocopherol or ascorbic acid. Proliferative, IFN-γ, IL-4, IL-10 and TGF-β responses were measured. In general, vitamin E supplementation was associated with a trend for reduced proliferative responses after stimulation with antigens and house dust mite, and with increased proliferation after stimulation with timothy grass allergen. There was a trend for CBMC cultures to exhibit decreased secretion of IFN-γ, IL-10 and IL-4. Supplementation with vitamin C had no effect on CBMC proliferation, but increased IFN-γ and IL-4 production, and decreased IL-10 production. In conclusion, in vitro vitamin E and C supplementation of CBMC modifies neonatal immune function, but not in a manner predicted by observational epidemiological studies. The observed associations between vitamin E and childhood respiratory disease are complex, and the nature and form of nutritional intervention need to be carefully considered before inclusion in trials.
References
[1]
Barker, R.N.; Burney, P.G.; Devereux, G.; Hardiman, M.; Holt, P.G.; O’Donnell, M.; Platts-Mills, T.A.; Seaton, A.; Strachan, D.P.; Weiss, S.T.; et al. The increase in allergic disease: Environment and susceptibility. Proceedings of a Symposium held at the Royal Society of Edinburgh, 4th June 2002. Clin. Exp. Allergy 2003, 33, 394–406, doi:10.1046/j.1365-2222.2003.01621.x.
[2]
Seaton, A.; Godden, D.J.; Brown, K. Increase in asthma: A more toxic environment or a more susceptible population? Thorax 1994, 49, 171–174, doi:10.1136/thx.49.2.171.
[3]
Devereux, G.; Seaton, A. Why don’t we give chest patients dietary advice? Thorax 2001, 56, ii15–ii22.
[4]
Malmberg, K.; Lenkei, R.; Petersson, M.; Ohlum, T.; Ichihara, F.; Glimelius, B.; Fr?din, J.E.; Masucci, G.; Kiessling, R. A short-term dietary supplementation of high doses of vitamin E increases T helper 1 cytokine production in patients with advanced colorectal cancer. Clin. Cancer Res. 2002, 8, 1772–1778.
[5]
Li-Weber, M.; Giaisi, M.; Treiber, M.K.; Krammer, P.H. Vitamin E inhibits IL-4 gene expression in peripheral blood T cells. Eur. J. Immunol. 2002, 32, 2401–2408, doi:10.1002/1521-4141(200209)32:9<2401::AID-IMMU2401>3.0.CO;2-S.
[6]
Dunstan, J.A.; Breckler, L.; Hale, J.; Lehmann, H.; Franklin, P.; Lyons, G.; Ching, S.Y.; Mori, T.A.; Barden, A.; Prescott, S.L. Supplementation with vitamins C, E, beta-carotene and selenium has no effect on anti-oxidant status and immune responses in allergic adults: A randomized controlled trial. Clin. Exp. Allergy 2007, 37, 180–187, doi:10.1111/j.1365-2222.2007.02657.x.
[7]
Yabuhara, A.; Macaubas, C.; Prescott, S.L.; Venaille, T.J.; Holt, B.J.; Habre, W.; Sly, P.D.; Holt, P.G. TH2-polarized immunological memory to inhalant allergens in atopics is established during infancy and early childhood. Clin. Exp. Allergy 1997, 27, 1261–1269, doi:10.1111/j.1365-2222.1997.tb01170.x.
[8]
Meydani, S.N.; Han, S.N.; Wu, D. Vitamin E and immune response in the aged: Molecular mechanisms and clinical implications. Immunol. Rev. 2005, 205, 269–284, doi:10.1111/j.0105-2896.2005.00274.x.
[9]
Litonjua, A.A.; Rifas-Shiman, S.L.; Ly, N.P.; Tantisira, K.G.; Rich-Edwards, J.W.; Camargo, C.A., Jr.; Weiss, S.T.; Gillman, M.W.; Gold, D.R. Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age. Am. J. Clin. Nutr. 2006, 84, 903–911.
[10]
Miyake, Y.; Sasaki, S.; Tanaka, K.; Hirota, Y. Consumption of vegetables, fruit, and antioxidants during pregnancy and wheeze and eczema in infants. Allergy 2010, 65, 758–765, doi:10.1111/j.1398-9995.2009.02267.x.
[11]
Devereux, G.; Turner, S.W.; Craig, L.C.; McNeill, G.; Martindale, S.; Harbour, P.J.; Helms, P.J.; Seaton, A. Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am. J. Respir. Crit. Care Med. 2006, 174, 499–507, doi:10.1164/rccm.200512-1946OC.
[12]
Devereux, G.; Barker, R.N.; Seaton, A. Antenatal determinants of neonatal immune responses to allergens. Clin. Exp. Allergy 2002, 32, 43–50, doi:10.1046/j.0022-0477.2001.01267.x.
[13]
Litonjua, A.A.; Tantisira, K.G.; Finn, P.W.; Schaub, B.; Schroeter, C.; Perkins, D.L. Maternal antioxidant intake during pregnancy and cord blood lymphoproliferative responses. Am. J. Respir. Crit. Care Med. 2004, 169, A501.
[14]
Weiss, S.T.; Litonjua, A.A. Maternal diet vs. lack of exposure to sunlight as the cause of the epidemic of asthma, allergies and other autoimmune diseases. Thorax 2007, 62, 746–748, doi:10.1136/thx.2007.079707.
[15]
Lawlor, D.A.; Davey Smith, G.; Kundu, D.; Bruckdorfer, K.R.; Ebrahim, S. Those confounded vitamins: What can we learn from the differences between observational vs. randomised trial evidence? Lancet 2004, 363, 1724–1727, doi:10.1016/S0140-6736(04)16260-0.
[16]
Devereux, G.; Hall, A.M.; Barker, R.N. Measurement of T-helper cytokines secreted by cord blood mononuclear cells in response to allergens. J. Immunol. Methods 2000, 234, 13–22, doi:10.1016/S0022-1759(99)00185-4.
[17]
Marshall, N.A.; Vickers, M.A.; Barker, R.N. Regulatory T cells secreting IL-10 dominate the immune response to EBV latent membrane protein 1. J. Immunol. 2003, 170, 6183–6189.
[18]
Scaife, A.R.; McNeill, G.; Campbell, D.; Martindale, S.; Devereux, G.; Seaton, A. Maternal intake of antioxidant vitamins in pregnancy in relation to maternal and fetal plasma levels at delivery. Br. J. Nutr. 2006, 95, 771–778, doi:10.1079/BJN20051718.
[19]
Miles, E.A.; Warner, J.A.; Jones, A.C.; Colwell, B.M.; Bryant, T.N.; Warner, J.O. Periperhal blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents. Clin. Exp. Allergy 1996, 26, 780–788, doi:10.1111/j.1365-2222.1996.tb00608.x.
[20]
Jones, A.C.; Miles, E.A.; Warner, J.O.; Colwell, B.M.; Bryant, T.N.; Warner, J.A. Fetal periperhal 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.
[21]
Beech, J.T.; Bainbridge, T.; Thompson, S.J. Incorporation of cells into an ELISA system enhances antigen-driven lymphokine detection. J. Immunol. Methods 1997, 205, 163–168, doi:10.1016/S0022-1759(97)00072-0.
[22]
Devereux, G. The increase in the prevalence of asthma and allergy: Food for thought. Nat. Rev. Immunol. 2006, 6, 869–874, doi:10.1038/nri1958.
[23]
Greenough, A.; Shaheen, S.O.; Shennan, A.; Seed, P.T.; Poston, L. Respiratory outcomes in early childhood following antenatal vitamin C and E supplementation. Thorax 2010, 65, 998–1003, doi:10.1136/thx.2010.139915.
[24]
Andreasyan, K.; Ponsonby, A.; Dwyer, T.; Kemp, A.; Dear, K.; Cochrane, J.; Carmichael, A. A differing pattern of association between dietary fish and allergen-specific subgroups of atopy. Allergy 2005, 60, 671–677, doi:10.1111/j.1398-9995.2005.00757.x.
[25]
Sakaguchi, S.; Miyara, M.; Costantino, C.M.; Hafler, D.A. FOXP3+ regulatory T cells in the human immune system. Nat. Rev. Immunol. 2010, 10, 490–500, doi:10.1038/nri2785.
[26]
Tan, P.H.; Sagoo, P.; Chan, C.; Yates, J.B.; Campbell, J.; Beutelspacher, S.C.; Foxwell, B.M.J.; Lombardi, G.; George, A.J.T. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J. Immunol. 2005, J174, 7633–7644.
[27]
Devereux, G.; Seaton, A.; Barker, R.N. University of Aberdeen, Aberdeen, UK, Unpublished work, 2002.
Hughes, D. Antioxidant Vitamins and Immune Function. In Nutrition and Immune Function; Calder, P.C., Field, C.J., Gill, H.S., Eds.; CABI Publishing: Wallingford, UK, 2002; p. 171.
[30]
Field, C.J.; Thomson, C.A.; van Aerde, J.E.; Parrott, A.; Euler, A.; Lien, E.; Clandinin, M.T. Lower proportion of CD45R0+ cells and deficient interleukin-10 production by formula-fed infants, compared with human-fed, is corrected with supplementation of long-chain polyunsaturated fatty acids. J. Pediatr. Gastroenterol. Nutr. 2000, 31, 291–299, doi:10.1097/00005176-200009000-00017.
[31]
Dunstan, J.A.; Mori, T.A.; Barden, A.; Beilin, L.J.; Taylor, A.L.; Holt, P.G.; Prescott, S.L. 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. 2003, 112, 1178–1184, doi:10.1016/j.jaci.2003.09.009.
[32]
Chi, A.; Wildfire, J.; McLoughlin, R.; Wood, R.A.; Bloomberg, G.R.; Kattan, M.; Gergen, P.; Gold, D.R.; Witter, F.; Chen, T.; et al. Umbilical cord plasma 25-hydroxyvitamin D concentration and immune function at birth: The Urban Environment and Childhood Asthma study. Clin. Exp. Allergy 2011, 41, 842–850, doi:10.1111/j.1365-2222.2011.03712.x.
[33]
Clark, J.; Craig, L.; McNeill, G.; Smith, N.; Norrie, J.; Devereux, G. A novel dietary intervention to optimize vitamin E intake of pregnant women to 15 mg/day. J. Acad. Nutr. Diet. 2012, 112, 297–301, doi:10.1016/j.jada.2011.08.033.