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

Velden, Vincent H.J. van der; Laan, M.P.; Baert, M.R.M.; Malefyt, René de Waal; Neijens, H. J.; Savelkoul, H.F.J.

doi:10.1046/j.1365-2222.2001.01176.x

Cited by 155 publications

(131 citation statements)

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“…At birth, possibly because of placenta-derived Th2 trophic factors, allergen-induced mononuclear cell responses are skewed toward a Th2-like phenotype (26,42), and IFN-γ responses are particularly low (43). While IL-13 secretion by CBMCs was correlated with a higher risk of atopic diseases (40,43), several studies have associated a reduced IFN-γ response at birth and a potential Th1/Th2 imbalance with the development of atopic manifestation in childhood (7,8,20,26,40,(43)(44)(45). The concept of a Th1/ Th2 imbalance with the demonstration of decreased Th1 and increased Th2 responses and therefore a pro-allergic phenotype is attractive.…”

Section: Discussionmentioning

confidence: 99%

“…One factor during the fetal period critical to the development of the immune system is exposure to different allergens, either in utero or postnatally. Antigen-induced proliferation by umbilical cord blood mononuclear cells (CBMCs) in response to a variety of antigens, including allergens, has been acknowledged in a number of studies (4)(5)(6) and has been associated with subsequent development of atopic diseases (7,8).…”

Section: Introductionmentioning

confidence: 99%

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Fetal Cord Blood: Aspects of Heightened Immune Responses

Schaub¹,

Tantisira

Gibbons

et al. 2005

J Clin Immunol

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Neonatal immune responses have been associated with the development of atopy in childhood. We assessed in cord blood mononuclear cells (CBMC) whether increased allergen/mitogen-induced lymphoproliferation (LP) is associated with pro-allergic Th2 cytokine IL-13 or Th1 cytokine IFN-γ secretion. We determined whether LP to one allergen is related to heightened lymphocyte function to other allergens/mitogen. CBMC from 135 neonates were stimulated with house dust mite (Derf1), cockroach, ovalbumin, or mitogen. LP to one allergen was associated with significantly increased LP to other allergens/mitogen. Increased Derf1-LP was associated with increased Derf1-induced IL-13 secretion (r = 0.21, p = 0.01). After adjusting for neonatal gender, race, and maternal smoking, Derf1-LP remained associated with Derf1-IL-13 (OR 3.08, 95% CI 1.56-6.10). Increased mitogeninduced proliferation was associated with increased mitogen-induced IL-13 secretion (r = 0.37, p < 0.001). For some individuals, a predisposition to a heightened immune response is already evident at birth. Whether this phenotype results in atopy in childhood warrants further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fetal Cord Blood: Aspects of Heightened Immune Responses

Schaub¹,

Tantisira

Gibbons

et al. 2005

J Clin Immunol

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“…Assim, a observação de presença desproporcional de CD45RO + no recém-nascido reflete resposta a estímulos antigênicos de origem intra-uterina 5,11,36 . Recentemente, demonstrou-se haver similaridade entre neonatos e adultos quanto à cinética de resposta à mudança de fenótipo CD45RA + para CD45RO + , ao primeiro estímulo com fito-hemaglutinina A (PHA) 35 , bem como aumento no percentual destas células (CD45RO+) no sangue de cordão umbilical de crianças que desenvolveram doença alérgica até o final do primeiro ano de vida 37 .…”

Section: Linfócitos Tunclassified

“…Recentemente, foi possível observar IL-4, IL-5 e IL-13 alérgeno-induzidas, mas não de INF-g, significativamente mais elevadas em sangue de cordão umbilical de neonatos que desenvolveram doença alérgica até a idade de um ano do que nos não alérgicos, que apresentaram apenas IL-10 em resposta ao estímulo alergênico, sugerindo a existência de defeito no mecanismo regulador da produção de INF-g 37 .…”

Section: Citocinasunclassified

Imunidade relacionada à resposta alérgica no início da vida

Correa¹,

Zuliani²

2001

J. Pediatr. (Rio J.)

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Objective: given that the most common allergic manifestations (asthma, rhinitis, dermatitis, food allergies) occur during childhood, because the immune system can be induced into sensitization rather than into allergenic tolerance at the beginning of life, we analyzed the main immunological aspects of fetuses and infant in terms of allergic sensitization and response.Methods: detailed bibliographic revision concerning nonspecific immune response (physical and chemical barriers, myeloid cells) and specific immune response (T and B lymphocytes, cytokines) of the fetus and infant, with special attention to studies carried out in the last fifteen years.Results: various compartments of the immune system in fetuses and infants are different from those present in older children and adults. Thus, developmental aspects of nonspecific and specific immunity may contribute to atopic disease.Conclusions: atopic predisposition is determined at the beginning of life and seems to originate not only from genetic factors, but also from intrauterine environment and initial stage of childhood, inducing the immune system to increase the synthesis of IgE.J Pediatr (Rio J) 2001; 77 (6): 441-6: hypersensitivity, autoimmunity, natural immunity, cellular immunity, antibody formation. ResumoObjetivo: considerando-se que é na infância que as manifestações alérgicas mais comuns (asma, rinite, dermatite, alergia alimentar) ocorrem, porque é no início da vida que o sistema imune pode ser induzido à sensibilização ao invés de tolerância alergênica, analisamos as principais peculiaridades imunológicas do feto e da criança jovem, inerentes à sensibilização e resposta alérgica.Métodos: os autores realizaram revisão literária detalhada concernente à resposta imune inespecífica (barreiras físico-químicas, células mielóides) e específica (linfócitos T e B, citocinas) do feto e de crianças mais jovens, enfatizando os estudos mais relevantes nos últimos quinze anos.Resultados: vários compartimentos do sistema imune do feto e de crianças mais jovens são diferentes daqueles da criança maior e do adulto. Conseqüentemente, aspectos relativos ao desenvolvimento da imunidade inespecífica e específica, podem contribuir para a geração de atopia.Conclusões: a predisposição atópica determina-se no início da vida e parece originar-se, além dos fatores genéticos, por aqueles ocorridos no ambiente intra-uterino e fase inicial da infância, os quais influenciam o sistema imune à síntese elevada de IgE.J Pediatr (Rio J) 2001; 77 (6): 441-6: hipersensibilidade, autoimunidade, imunidade natural, imunidade celular, formação de anticorpos. Imunidade relacionada à resposta alérgica no início da vidaImmunity related to allergic response at the beginning of life Joaquina M.M. Correa 1 , Antonio Zuliani 2 As alergopatias resultam de uma conjunção de fatores genéticos (produção de células, citocinas e imunoglobulina E, por exemplo) e ambientais específicos (alérgenos) ou inespecíficos (tabagismo, infecções, exercícios, alterações psicossociais, tratamento e outros). T...

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“…For example, a decreased production of allergen-induced IFN-␥ by CB mononuclear cells (CBMCs) is associated with allergy development (5,6). Furthermore, the Th1/Th2 balance in vivo has shown to be Th2-biased at birth in children who develop allergic disease later in life (7,8).…”

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confidence: 99%

High Cord Blood Levels of the T-Helper 2-Associated Chemokines CCL17 and CCL22 Precede Allergy Development During the First 6 Years of Life

et al. 2011

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Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1-and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life. (Pediatr Res 70: 495-500, 2011)

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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

Cited by 155 publications

References 40 publications

Fetal Cord Blood: Aspects of Heightened Immune Responses

Fetal Cord Blood: Aspects of Heightened Immune Responses

Imunidade relacionada à resposta alérgica no início da vida

High Cord Blood Levels of the T-Helper 2-Associated Chemokines CCL17 and CCL22 Precede Allergy Development During the First 6 Years of Life

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