Abstract
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.
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Abbreviations
- Th:
-
T-helper
- TGF-β:
-
transforming growth factor-β
- IFN-γ:
-
interferon-γ
- sIg:
-
secretory immunoglobulin
- SC:
-
secretory component
- HSA:
-
human serum albumin
- PHT:
-
PBS with 0.05% Tween and 0.5% HSA
- pNPP:
-
p-nitrophenyl phosphate
References
Hattevig G, Kjellman B, Björkstén B 1993 Appearance of IgE antibodies to ingested and inhaled allergens during the first 12 years of life in atopic and non-atopic children. Pediatr Allergy Immunol 4: 182–186.
Billington WD 1992 The normal fetomaternal immune relationship. Clin Obstet Gynecol 6: 417–438.
Orlando S 1995 The immunologic significance of breast milk. J Obstet Gynecol Neonatal Nurs 24: 678–683.
Goldman AS 1993 The immune system of human milk: antimicrobial, antiinflammatory and immunomodulating properties. Pediatr Infect Dis J 12: 664–671.
Goldman AS, Chheda S, Garofalo R, Schmalstieg FC 1996 Cytokines in human milk: properties and potential effects upon the mammary gland and the neonate. J Mammary Gland Biol Neoplasia 1: 251–258.
Buescher ES, Malinowska I 1996 Soluble receptors and cytokine antagonists in human milk. Pediatr Res 40: 839–844.
Bessler H, Straussberg R, Hart J, Notti I, Sirota L 1996 Human colostrum stimulates cytokine production. Biol Neonate 69: 376–382.
Saarinen UM, Kajoraari M 1995 Breastfeeding as prophylaxis against atopic disease: prospective follow-up study until 17 years old. Lancet 346: 1065–1069.
van Asperen PP, Kemp AS, Mellis CM 1984 Relationship of the diet in the development of atopy in infancy. Clin Allergy 14: 525–532.
Romagnani S 1994 Lymphokine production by human T cells in disease states. Annu Rev Immunol 12: 227–257.
Venge J, Lampinen M, Håkansson L, Rak S, Venge P 1996 Identification of IL-5 and RANTES as a major eosinophil chemoattractants in the asthmatic lung. J Allergy Clin Immunol 97: 1110–1115.
Yamaguchi Y, Suda T, Ohta S, Tominaga K, Miura Y, Kasahara T 1991 Analysis of the survival of mature human eosinophils: interleukin-5 prevents apoptosis in mature human eosinophils. Blood 78: 2542–2547.
Horie S, Gleich GJ, Kita H 1996 Cytokines directly induce degranulation and superoxide production from human eosinophils. J Allergy Clin Immunol 98: 371–381.
Pène JF, Rousset F, Brière F, Chrétien I, Bonnefoy J-Y, Spits H, Yokota T, Aral K-I, Bancherau J, de Vries JE 1988 IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons γ and α and prostaglandin E2 . Proc Natl Acad Sci U S A 85: 6880–6884.
Vercelli D, Jabara HH, Arai K-I, Yokota T, Geha RS 1989 Endogenous interleukin 6 plays an obligatory role in interleukin 4-dependent human IgE synthesis. Eur J Immunol 19: 1419–1424.
Punnonen J, de Waal Malefyt R, van Vlasselaer P, Gauchat J-F, de Vriers JE 1993 IL-10 and viral IL-10 prevent induced IgE synthesis by inhibiting the accessory cell function of monocytes. J Immunol 151: 1280–1289.
Wu YC, Brinkmann V, Cox D, Heusser C, Delespess G 1992 Modulation of human IgE synthesis by transforming growth factor-β. Clin Immunol Immunopathol 62: 277–284.
Renz H, Vestner R, Petzoldt S, Brehler C, Prinz H, Rieger CHL 1990 Elevated concentrations of salivary secretory immunoglobulin A anti-cow's milk protein in newborns at risk of allergy. Int Arch Allergy Appl Immunol 92: 247–253.
Srivastava MD, Srivastava A, Brouhard B, Saneto R, Groh-Wargo S, Kubit J 1996 Cytokines in human milk. Res Commun Mol Pathol Pharmacol 93: 263–287.
Kropf J, Schurek JO, Wollner A, Gressner AM 1997 Immunological measurement of transforming growth factor-beta I (TGF-βI) in blood; assay development and comparison. Clin Chem 43: 1965–1974.
Kulkarni AB, Karlsson S 1993 Transforming growth factor-β1 knockout mice: a mutation in one cytokine gene causes a dramatic inflammatory disease. Am J Pathol 143: 3–9.
Koletzko S, Sherman P, Corey M, Griffiths A, Smith C 1989 Role of infant feeding practices in development of Crohn's disease in childhood. BMJ 298: 1617–1618.
Mayer EJ, Hamman RF, Gay EC, Lezotte DC, Savitz DA, Klingensmith GJ 1988 Reduced risk of IDDM among breast fed children. Diabetes 37: 1625–1632.
Björkstén B 1983 Does breast feeding prevent the development of allergy?. Immunol Today 4: 215–217.
Tilg H, Dinarello CA, Mier JW 1997 IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 18: 428–432.
Fujihashi K, McGhee JR, Lue C, Beagley KW, Taga T, Hirano T, Kishimoto T, Mestecky J, Kiyono H 1991 Human appendix B cells naturally express receptors for and respond to interleukin 6 with selective IgA1 and IgA2 synthesis. J Clin Invest 88: 248–252.
Defrance T, Vanbervliet B, Brière F, Durand I, Rousset F, Banchereau J 1992 Interleukin 10 and transforming growth factor β cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A. J Exp Med 175: 671–682.
Meillet D, Labrousse F, Benoit MO, Hernvann A, Musset L, Van Amerongen G 1997 Increased serum concentration of IgA2 subclass and IgA2/IgA1 ratio: specific markers of chronic alcoholic abuse?. Eur J Clin Chem Clin Biochem 35: 275–279.
Avanzini MA, Plebani A, Monafo V, Pasinetti G, Teani M, Colombo A, Mellander L, Carlsson B, Hanson LÅ, Ugazio AG, Burgio GR 1992 A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life. Acta Paediatr 81: 296–301.
Fitszimmons SP, Evans MK, Pearce CL, Sheridan MJ, Wientzen R, Cole MF 1994 Immunoglobulin A subclasses in infants' saliva and in saliva and milk from their mothers. J Pediatr 124: 566–573.
Garofalo R, Chheda S, Mei F, Palkowetz KH, Rudloff HE, Schmalstieg FC, Rassin DK, Goldman AS 1995 Interleukin-10 in human milk. Pediatr Res 37: 444–449.
Sone S, Tsutsumi H, Takeuchi R, Matsuda K, Imai S, Ogra PL, Chiba S 1997 Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus. J Leukoc Biol 61: 630–636.
Rudloff S, Niehues T, Rutsch M, Kunz C, Schroten H 1999 Inflammation markers and cytokines in breast milk of atopic and non-atopic women. Allergy 54: 206–211.
Basolo F, Conaldi PG, Fiore L, Calvo S, Toniolo A 1993 Normal breast epithelial cells produce interleukins 6 and 8 together with tumor-necrosis factor: defective IL6 expression in mammary carcinoma. Int J Cancer 55: 926–930.
Bocci V, von Bremen K, Corradeschi F, Franchi F, Luzzi E, Paulesu L 1993 Presence of interferon-γ and interleukin-6 in colostrum of normal women. Lymphokine Cytokine Res 12: 21–24.
Eglinton BA, Roberton DM, Cummins AG 1994 Phenotype of T cells, their soluble receptor levels, and cytokine profile of human breast milk. Immunol Cell Biol 72: 306–313.
Allardyce RA, Wilson A 1984 Breast milk supernatants from atopic donors stimulate cord blood IgE secretion in vitro. Clin Allergy 1984: 259–267.
Ehlers S, Smith KA 1991 Differentiation of T cell lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med 173: 25–36.
Rudloff HE, Schmalstieg FC, Palkowetz KH, Paskiewicz EJ, Goldman AS 1993 Interleukin-6 in human milk. J Reprod Immunol 23: 13–20.
Acknowledgements
The authors thank Dr. Armond Goldman for kindly providing colostrum samples and for helpful discussions and Ulrika Leek and Lena Lindell for excellent technical assistance.
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Supported by the Swedish Medical Research Council (grant 7510), the Vårdal Foundation, the Foundation for Strategic Research, the National Swedish Association against Allergic disease, the National Heart and Lung association, and Glaxo-Wellcome.
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Böttcher, M., Jenmalm, M., Garofalo, R. et al. Cytokines in Breast Milk from Allergic and Nonallergic Mothers. Pediatr Res 47, 157 (2000). https://doi.org/10.1203/00006450-200001000-00026
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DOI: https://doi.org/10.1203/00006450-200001000-00026
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