Abstract
To determine some early signs connected with the increased risk of future allergy development, gene expression and production of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children and support thus their easier allergization. Allergic phenotype pointing to the bias to TH2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as a predictive sign of increased allergy risk.
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Abbreviations
- AM:
-
allergic mothers
- CBC:
-
cord blood cell(s)
- CBML:
-
cord blood mononuclear leukocytes
- CV:
-
coefficient of variance
- HM:
-
healthy mothers
- RT:
-
real-time (PCR)
References
Benn C.S., Wohlfahrt J., Aaby P., Westergaard T., Benfeldt E., Michaelsen K.F., Björkstén B., Melbye M.: Breastfeeding and risk of atopic dermatitis, by parental history of allergy, during the first 18 months of life. Am.J.Epidemiol.160, 217–223 (2004).
Chung E.K., Miller R.L., Wilson M.T., Mcgeady S.J., Culhane J.F.: Antenatal risk factors, cytokines and the development of atopic disease in early childhood. Arch.Dis.Child.Fetal.Neonatal. Ed. 92, F68–F73 (2007).
Contreras J.P., Ly N.P., Gold D.R., He H., Wand M., Weiss S.T., Perkins D.L., Platts-Mills T.A., Finn P.W.: Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children. J.Allergy Clin.Immunol.112, 1072–1077 (2003).
Fayette J., Dubois B., Vandenabeele S., Bridon J.M., Vanbervliet B., Durand I., Banchereau J., Caux C., Briere F.: Human dendritic cells skew isotype switching of CD40-activated naïve B cells towards IgA1 and IgA2. J.Exp.Med.185, 1909–1918 (1997).
Graves P.E., Kabesch M., Halonen M., Holberg C.J., Baldini M., Fritsch C., Weiland S.K., Erickson R.P., von Mutius E., Martinez F.D.: A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children. J.Allergy Clin.Immunol.105, 506–513 (2000).
Hauer A.C., Riederer M., Griessl A., Rosegger H., Macdonald T.T.: Cytokine production by cord blood mononuclear cells stimulated with cows milk proteins in vitro: interleukin-4 and transforming growth factor β-secreting cells detected in the CD45RO T cell population in children of atopic mothers. Clin.Exp.Allergy33, 615–623 (2003).
Jutel M., Akdis M., Budak F., Aebicher-Casaulta C., Wrzyszcz M., Blaser K., Akdis C.A.: IL-10 and TGF-β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur.J.Immunol.33, 1205–1214 (2003).
Kondo N., Kobayashi Y., Shinoda S., Takenaka R., Teramoto T., Kaneko H., Fukao T., Matsui E., Kasahara K., Yokoyama Y.: Reduced interferon γ production by antigen-stimulated cord blood mononuclear cells is a risk factor of allergic disorders — 6-year follow-up study. Clin.Exp.Allergy28, 1340–1344 (1998).
Mcgee D.W., Beagley K.W., Aicher W.K., Mcghee J.R.: Transforming growth factor-β enhances interleukin-6 secretion by intestinal epithelial cells. Immunology77, 7–12 (1992).
Mohamed M.A., Cunningham-Rundles S., Dean C.R., Hammad T.A., Nesin M.: Levels of pro-inflammatory cytokines produced from cord blood in-vitro are pathogen dependent and increased in comparison to adult controls. Cytokine39, 171–177 (2007).
Nair R.R., Warner B.B., Warner B.W.: Role of epidermal growth factor and other growth factors in the prevention of necrotizing enterocolitis. Semin.Perinatol.32, 107–113 (2008).
Ohshima Y., Yasutomi M., Omata N., Yamada A., Fujisawa K., Kasuga K., Hiraoka M., Mayumi M.: Dysregulation of IL-13 production by cord blood CD4+ T cells is associated with the subsequent development of atopic disease in infants. Pediatr. Res.51, 195–200 (2002).
Peden D.B.: The epidemiology and genetics of asthma risk associated with air pollution. J.Allergy Clin.Immunol.115, 213–219 (2005).
Prescott S.L., Macaubas C., Smallacombe T., Holt B.J., Sly P.D., Loh R., Holt P.G.: Reciprocal age-related patterns of allergen-specific T-cell immunity in normal vs. atopic infants. Clin.Exp.Allergy28(Suppl. 5), 39–44 (1998).
Prescott S.L., King B., Strong T.L., Holt P.G.: The value of perinatal immune responses in predicting allergic disease at 6 years of age. Allergy58, 1187–1194 (2003).
Schaub B., Tantisira K.G., Gibbons F.K., He H., Litonjua A.A., Gillman M.W., Weiss S., Perkins D.L., Gold D.R., Finn P.W.: Fetal cord blood: aspects of heightened immune responses. J.Clin.Immunol.25, 329–337 (2005).
Silberer J., Ihorst G., Kopp M.V.: Cytokine levels in supernatants of whole blood and mononuclear cell cultures in adults and neonates reveal significant differences with respect to interleukin-13 and interferon-γ. Pediatr.Allergy Immunol.19, 140–147 (2008).
Steinke J.W., Rich S.S., Borish L.: Genetics of allergic disease. 5. J.Allergy Clin.Immunol.121, S384–S387 (2008).
Tadaki H., Arakawa H., Sugiyama M., Ozawa K., Mizuno T., Mochizuki H., Tokuyama K, Morikawa A.: Association of cord blood cytokine levels with wheezy infants in the first year of life. Pediatr.Allergy Immunol.20, 227–233 (2009).
Tanaka K., Sugiura H., Uehara M., Hashimoto Y., Donnelly C., Montgomery D.S.: Lack of association between atopic eczema and the genetic variants of interleukin-4 and the interleukin-4 receptor α chain gene: heterogeneity of genetic backgrounds on immunoglobulin E production in atopic eczema patients. Clin.Exp.Allergy31, 1522–1527 (2001).
van der Veden V., Laan M.P., Baert M.R., de Waal M.R., Neijens H.J., Savelkoul H.F.: Selective development of a strong TH2 cytokine profile in high-risk children who develop atopy: risk factors and regulatory role of IFN-γ, IL-4 and IL-10. Clin.Exp.Allergy31, 997–1006 (2001).
Wang J.Y., Lin C.G., Bey M.S., Bey M.S., Wang L., Lin F.Y., Huang L., Wu L.S.: Discovery of genetic difference between asthmatic children with high IgE level and normal IgE level by whole genome linkage disequilibrium mapping using 763 autosomal STR markers. J.Hum.Genet.50, 249–258 (2005).
Žižka J., Hrdý J., Lodinová-Žádníková R., Kocourková I., Novotná O., Šterzl I., Prokešová L.: Effect of breast milk of healthy and allergic mothers on in vitro stimulation of cord blood lymphocytes. Pediatr.Allergy Immunol.18, 486–494 (2007).
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Hrdý, J., Zanvit, P., Novotná, O. et al. Cytokine expression in cord blood cells of children of healthy and allergic mothers. Folia Microbiol 55, 515–519 (2010). https://doi.org/10.1007/s12223-010-0085-7
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DOI: https://doi.org/10.1007/s12223-010-0085-7