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Immunological factors in breast milk in relation to allergy in mother and child
Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
2002 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Background: The allergy preventive effect of breast-feeding against the development of allergy is controversial and some of this controversy may be due to differences in the composition of breast milk between different mothers.

Aim: To analyse IgA, cytokine and chemokines levels in human milk and relate the findings to matemal allergy and to development of atopic disease and IgA production in the infants, and furthermore, to assess the effects of breast milk on CBMC cytokine production. To approach these aims, several assays and methods had to be developed.

Material and Methods: The levels of total IgA, secretory IgA and ß-lactoglobulin, ovalbumin and Fel d 1 specific IgA antibodies in breast milk and saliva, as well as IL- 4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-ß, eotaxin, MIP-1α and RANTES in breast milk were analysed by ELISA. Cytokine responses from phytohaemagglutinin, cat dander or ovalbumin stimulated cord blood mononuclear cells were studied in the absence or presence of colostrum.

Results: The composition of immunological factors in breast milk varied widely between different mothers. The levels of secretory IgA and ß-lactoglobulin and ovalbumin specific IgA were higher in breast milk from non-allergic than allergic mothers. On the other hand, allergic mothers had higher levels of IL-4, IL-8 and RANTES in their breast milk. There were no relation between the levels of secretory IgA, cytokines and chemokines in breast milk and the development of atopic disease and salivary IgA production in the infants, however. Colostrum inhibited phytohaemagglutinin induced IFN-γ and IL-4 production and cat dander induced IFN-γ production. In contrast, allergen induced IL-5, IL-10 and IL-13 production was enhanced by colostrum. The effects of breast milk on cytokine production were independent of the atopic status of the mothers. The inhibiting effect of colostrum on phytohaemagglutinin induced IFN-γ production correlated with breast milk TGF-β levels, and was partly blocked by the addition of an anti-TGF-ß antibody.

Conclusion: There were great individual variations regarding the levels of total and allergen specific IgA, cytokines and chemokines in human milk. Furthermore, breast milk from allergic and non-allergic mothers differed in several aspects. These differences seemed to be of minor importance for the development of atopic disease and IgA production in the breast-fed infant up to two years of age, however. The composition of human milk and the observed effects of breast milk on allergen and mitogen induced cytokine production confirms the anti-inflammatmy properties of human milk, and also suggest possible mechanisms whereby breast-feeding may protect against development of atopic disease. Our results do not support that the effects of breast-feeding are dependent on differences in the immunological composition of the milk, however.

Ort, förlag, år, upplaga, sidor
Linköping: Linköpings universitet , 2002. , s. 53
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 724
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-26650Lokalt ID: 11215ISBN: 91-7373-168-4 (tryckt)OAI: oai:DiVA.org:liu-26650DiVA, id: diva2:247199
Disputation
2002-04-12, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Svenska)
Opponent
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2012-09-14Bibliografiskt granskad
Delarbeten
1. Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk
Öppna denna publikation i ny flik eller fönster >>Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk
2000 (Engelska)Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 105, nr 6 part 1, s. 1236-1240Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.

Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.

Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.

Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).

Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-25825 (URN)10.1067/mai.2000.105805 (DOI)10262 (Lokalt ID)10262 (Arkivnummer)10262 (OAI)
Forskningsfinansiär
Vetenskapsrådet, 7510
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2021-02-25Bibliografiskt granskad
2. Cytokines in breast milk from allergic and nonallergic mothers
Öppna denna publikation i ny flik eller fönster >>Cytokines in breast milk from allergic and nonallergic mothers
2000 (Engelska)Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, nr 1, s. 157-162Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-25827 (URN)10.1203/00006450-200001000-00026 (DOI)10264 (Lokalt ID)10264 (Arkivnummer)10264 (OAI)
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
3. Chemoattractant factors in breast milk from allergic and nonallergic mothers
Öppna denna publikation i ny flik eller fönster >>Chemoattractant factors in breast milk from allergic and nonallergic mothers
2000 (Engelska)Ingår i: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 47, nr 5, s. 592-597Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1α, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-49768 (URN)10.1203/00006450-200005000-00006 (DOI)
Tillgänglig från: 2009-10-11 Skapad: 2009-10-11 Senast uppdaterad: 2017-12-12Bibliografiskt granskad
4. Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production
Öppna denna publikation i ny flik eller fönster >>Effects of breast milk from allergic and non-allergic mothers on mitogen- and allergen-induced cytokine production
2003 (Engelska)Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 1, s. 27-34Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. The aim of this study was to analyze the effects of breast milk, on mitogen- and allergen-induced cytokine production from cord blood mononuclear cells (CBMC), and if those effects differ between allergic and non-allergic mothers. The cells were incubated for 96 h with phytohemagglutinin (PHA), ovalbumin or cat dander in the presence of various dilutions of colostrum. Colostrum inhibited both mitogen- and cat-induced IFN-γ and mitogen-induced interleukin-4 (IL-4) production. The inhibition on IFN-γ production was to some extent caused by TGF-β, as the effect was modified when an anti-TGF-β antibody was added to the cultures. In contrast, colostrum enhanced allergen-induced production of the Th2-like cytokines IL-5 and IL-13, and this was accompanied with increased production of IL-10. No differences were found between allergic and non-allergic mothers. The inhibitory effect of breast milk on IFN-γ production, which was partly due to the high levels of TGF-β, together with the enhancing effect on IL-10 secretion, confirm that breast milk is anti-inflammatory. Although the production of IL-5 and IL-13 was enhanced by colostrum, this was accompanied with an increased production of IL-10. Together with the high levels of TGF-β in breast milk and inhibitory effect of colostrum on IL-4 production, this suggests a possible mechanism whereby breast-feeding may protect against the development of allergy. Despite differences in the composition of breast milk between allergic and non-allergic mothers, the effects of breast milk on cytokine production from CBMC were independent of the atopic status of the mothers.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-26400 (URN)10.1034/j.1399-3038.2003.02119.x (DOI)000181109600005 ()12603708 (PubMedID)10938 (Lokalt ID)10938 (Arkivnummer)10938 (OAI)
Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
5. Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants
Öppna denna publikation i ny flik eller fönster >>Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants
2003 (Engelska)Ingår i: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 14, nr 1, s. 35-41Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.

Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-26398 (URN)10.1034/j.1399-3038.2003.02120.x (DOI)10936 (Lokalt ID)10936 (Arkivnummer)10936 (OAI)
Anmärkning

On the day of the defence day the status of this article was submitted.

Tillgänglig från: 2009-10-08 Skapad: 2009-10-08 Senast uppdaterad: 2017-12-13Bibliografiskt granskad

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