Breast-feeding, atopy, and asthma

Abstract

To the Editor:Recent reports by Chulada et al1.Chulada P.C Arbes Jr., S.J Dunson D Zeldin D.C Breast-feeding and the prevalence of asthma and wheeze in children from the third national health and nutrition examination survey, 1988-1994.J Allergy Clin Immunol. 2003; 111: 328-336Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and several others2.Dell S To T Breastfeeding and asthma in young children: findings from a population-based study.Arch Pediatr Adolesc Med. 2001; 155: 1261-1265Crossref PubMed Google Scholar, 3.Romieu I Werneck G Ruiz Velasco S White M Hernandez M Breastfeeding and asthma among Brazilian children.J Asthma. 2000; 37: 575-583Crossref PubMed Scopus (21) Google Scholar, 4.Oddy W.H Holt P.G Sly P.D Read A.W Landau L.I Stanley F.J et al.Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study.BMJ. 1999; 319: 815-819Crossref PubMed Scopus (416) Google Scholar showed a protective effect of exclusive breast-feeding of ≥4 months against asthma and atopy, though some studies did not support this conclusion.5.Rust G.S Thompson C.J Minor P Davis-Mitchell W Holloway K Murray V Does breastfeeding protect children from asthma? Analysis of NHANES III survey data.J Natl Med Assoc. 2001; 93: 139-148PubMed Google Scholar What could be the reason for these controversial findings?Normally, a balance is maintained between TH1 and TH2 cells. TH1 cells produce IFN-γ, IL-2, and TNF-α, whereas TH2 cells produce IL-4, IL-10, and IL-13 cytokines. IFN-γ is a pleiotropic cytokine that acts by binding to its receptor, which is coupled to the Jak-STAT signaling pathway. Animals that lack IFN-γ, the IFN-γ receptor, or STAT 1 display disruption of both innate and adaptive immunity. T-bet, a member of the T-box family of transcription factors, is rapidly induced in early developing TH1 cells and is absent in developing TH2 cells. Introduction of T-bet into T cells results in the conversion of these cells into TH1 cells that produce IFN-γ but not IL-4 and IL-5 production.6.Szabo S Sullivan B.M Stemmann C Satoskar A.R Sleckman B.P Glimcher L.H Distinct effects of T-bet in TH1 lineage commitment and IFN-γ production in CD4 and CD8 T cells.Science. 2002; 295: 338-342Crossref PubMed Scopus (966) Google Scholar Mice that lack T-bet cannot generate TH1 response and have development of spontaneous airway hyperreactivity and asthma.7.Finotto S Neurath M.F Glickman J.N Qin S Lehr H.A Green F.H et al.Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.Science. 2002; 295: 336-338Crossref PubMed Scopus (538) Google ScholarBreast milk is rich in long-chain polyunsaturated fatty acids (LCPUFAs).8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar LCPUFAs, especially γ-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suppress immune response and the secretion of TH1 cytokines IL-1, IL-2, and TNF-α. The inhibitory effect of EPA and DHA on the secretion of IL-1, IL-2, and TNF-α are much stronger than those exerted by GLA and AA. Synthesis and secretion of TNF-α is diminished by EPA and DHA and is unchanged or increased by AA and other ω-6 fatty acids. Furthermore, EPA/DHA supplementation enhances transforming growth factor (TGF)–β production and thus delayed autoimmune disease in experimental animals. TGF-β decreases biosynthesis and release of TNF-α and thus serves as a negative controller of TNF-α production. Some of the actions of TGF-β depend on the presence of LCPUFAs.8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Thus, depending on the type and amounts of LCPUFAs given, TH1 responses can be enhanced and TH2 responses are blunted, which favor suppression of atopy and asthma. This favorable action on TH1 and TH2 responses may depend on the ratio between ω-3 and ω-6 fatty acids. A higher ratio of ω-6 to ω-3 LCPUFAs favors an enhancement in the TH1 response, whereas a decrease in the ratio between ω-6 to ω-3 may favor the TH2 response. Because breast milk is rich in ω-6 LCPUFAs, the protective effect of breast-feeding against atopy and asthma might be attributed to its high content of these beneficial fatty acids.8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar This is supported by the observation of Galli et al,9.Galli E Picardo M Chini L Passi S Moschese V Terminali O et al.Analysis of polyunsaturated fatty acids in newborn sera: a screening tool for atopic disease?.Br J Dermatol. 1994; 130: 752-756Crossref PubMed Scopus (69) Google Scholar who showed that in newborn infants “at risk” for atopic disease, di-homo-gamma-linolenic acid and AA levels were lower in cord blood in infants who subsequently had atopic disease than in nonatopic infants. These changes were more marked in children who subsequently had atopic disease.It is suggested that duration of breast-feeding and LCPUFA content of breast milk are two variables that may account for differences in the results reported by various investigators. It is likely that there is a linear relation between the concentrations of ω-6 and ω-3 fatty acids and TGF-β in human breast milk, which may explain the significant inverse association observed between the dose of TGF-β received through milk and wheezing.10.Oddy W.H Halonen M Martinez F.D Lohman I.C Stern D.A Kurzius-Spencer M et al.TGF-β in human milk is associated with wheeze in infancy.J Allergy Clin Immunol. 2003; 112: 723-728Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar Hence, in the future, not only the duration of breast-feeding but also the LCPUFA and TGF-β content and the ratio between various LCPUFAs and TGF-β in breast milk and their relation to atopy and asthma and the effect of various LCPUFAs on T-bet expression need to be studied. To the Editor: Recent reports by Chulada et al1.Chulada P.C Arbes Jr., S.J Dunson D Zeldin D.C Breast-feeding and the prevalence of asthma and wheeze in children from the third national health and nutrition examination survey, 1988-1994.J Allergy Clin Immunol. 2003; 111: 328-336Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and several others2.Dell S To T Breastfeeding and asthma in young children: findings from a population-based study.Arch Pediatr Adolesc Med. 2001; 155: 1261-1265Crossref PubMed Google Scholar, 3.Romieu I Werneck G Ruiz Velasco S White M Hernandez M Breastfeeding and asthma among Brazilian children.J Asthma. 2000; 37: 575-583Crossref PubMed Scopus (21) Google Scholar, 4.Oddy W.H Holt P.G Sly P.D Read A.W Landau L.I Stanley F.J et al.Association between breast feeding and asthma in 6 year old children: findings of a prospective birth cohort study.BMJ. 1999; 319: 815-819Crossref PubMed Scopus (416) Google Scholar showed a protective effect of exclusive breast-feeding of ≥4 months against asthma and atopy, though some studies did not support this conclusion.5.Rust G.S Thompson C.J Minor P Davis-Mitchell W Holloway K Murray V Does breastfeeding protect children from asthma? Analysis of NHANES III survey data.J Natl Med Assoc. 2001; 93: 139-148PubMed Google Scholar What could be the reason for these controversial findings? Normally, a balance is maintained between TH1 and TH2 cells. TH1 cells produce IFN-γ, IL-2, and TNF-α, whereas TH2 cells produce IL-4, IL-10, and IL-13 cytokines. IFN-γ is a pleiotropic cytokine that acts by binding to its receptor, which is coupled to the Jak-STAT signaling pathway. Animals that lack IFN-γ, the IFN-γ receptor, or STAT 1 display disruption of both innate and adaptive immunity. T-bet, a member of the T-box family of transcription factors, is rapidly induced in early developing TH1 cells and is absent in developing TH2 cells. Introduction of T-bet into T cells results in the conversion of these cells into TH1 cells that produce IFN-γ but not IL-4 and IL-5 production.6.Szabo S Sullivan B.M Stemmann C Satoskar A.R Sleckman B.P Glimcher L.H Distinct effects of T-bet in TH1 lineage commitment and IFN-γ production in CD4 and CD8 T cells.Science. 2002; 295: 338-342Crossref PubMed Scopus (966) Google Scholar Mice that lack T-bet cannot generate TH1 response and have development of spontaneous airway hyperreactivity and asthma.7.Finotto S Neurath M.F Glickman J.N Qin S Lehr H.A Green F.H et al.Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet.Science. 2002; 295: 336-338Crossref PubMed Scopus (538) Google Scholar Breast milk is rich in long-chain polyunsaturated fatty acids (LCPUFAs).8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar LCPUFAs, especially γ-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), suppress immune response and the secretion of TH1 cytokines IL-1, IL-2, and TNF-α. The inhibitory effect of EPA and DHA on the secretion of IL-1, IL-2, and TNF-α are much stronger than those exerted by GLA and AA. Synthesis and secretion of TNF-α is diminished by EPA and DHA and is unchanged or increased by AA and other ω-6 fatty acids. Furthermore, EPA/DHA supplementation enhances transforming growth factor (TGF)–β production and thus delayed autoimmune disease in experimental animals. TGF-β decreases biosynthesis and release of TNF-α and thus serves as a negative controller of TNF-α production. Some of the actions of TGF-β depend on the presence of LCPUFAs.8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Thus, depending on the type and amounts of LCPUFAs given, TH1 responses can be enhanced and TH2 responses are blunted, which favor suppression of atopy and asthma. This favorable action on TH1 and TH2 responses may depend on the ratio between ω-3 and ω-6 fatty acids. A higher ratio of ω-6 to ω-3 LCPUFAs favors an enhancement in the TH1 response, whereas a decrease in the ratio between ω-6 to ω-3 may favor the TH2 response. Because breast milk is rich in ω-6 LCPUFAs, the protective effect of breast-feeding against atopy and asthma might be attributed to its high content of these beneficial fatty acids.8.Das U.N Essential fatty acids as possible enhancers of the beneficial actions of probiotics.Nutrition. 2002; 18: 786-789Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar This is supported by the observation of Galli et al,9.Galli E Picardo M Chini L Passi S Moschese V Terminali O et al.Analysis of polyunsaturated fatty acids in newborn sera: a screening tool for atopic disease?.Br J Dermatol. 1994; 130: 752-756Crossref PubMed Scopus (69) Google Scholar who showed that in newborn infants “at risk” for atopic disease, di-homo-gamma-linolenic acid and AA levels were lower in cord blood in infants who subsequently had atopic disease than in nonatopic infants. These changes were more marked in children who subsequently had atopic disease. It is suggested that duration of breast-feeding and LCPUFA content of breast milk are two variables that may account for differences in the results reported by various investigators. It is likely that there is a linear relation between the concentrations of ω-6 and ω-3 fatty acids and TGF-β in human breast milk, which may explain the significant inverse association observed between the dose of TGF-β received through milk and wheezing.10.Oddy W.H Halonen M Martinez F.D Lohman I.C Stern D.A Kurzius-Spencer M et al.TGF-β in human milk is associated with wheeze in infancy.J Allergy Clin Immunol. 2003; 112: 723-728Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar Hence, in the future, not only the duration of breast-feeding but also the LCPUFA and TGF-β content and the ratio between various LCPUFAs and TGF-β in breast milk and their relation to atopy and asthma and the effect of various LCPUFAs on T-bet expression need to be studied.