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Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis

M E Belderbos1, E F Knol, M L Houben

  • 1Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
|November 19, 2011
PubMed

Insights

Neonatal immune responses, specifically Toll-like receptor (TLR)-mediated cytokine production, are linked to early-life atopic dermatitis (AD) but not respiratory syncytial virus lower respiratory tract infection (RSV LRTI). Lower IL-10 production in newborns may contribute to AD development.

Area of Science:

  • Immunology
  • Pediatrics
  • Allergy

Background:

  • Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are prevalent in early childhood.
  • Impaired Toll-like receptor (TLR)-mediated Th1-cell responses are implicated in the pathogenesis of both conditions.
  • Neonatal TLR-mediated Th1-type cytokine production increases significantly within the first month of life.

Purpose of the Study:

  • To investigate the association between reduced TLR-mediated production of Th1-polarizing cytokines at one month of age and the subsequent development of AD or RSV LRTI.
  • To identify potential pre-symptomatic immune markers for these common early-life diseases.

Main Methods:

  • A prospective cohort study involving 291 neonates.
  • Measurement of innate immune cell concentrations and TLR-mediated cytokine responses in whole blood at one month of age.
  • Diagnosis of AD via physician questionnaire at one year; RSV LRTI diagnosis based on parental report and RSV RNA detection.

Main Results:

  • AD developed in 15% and RSV LRTI in 14% of neonates; no association was found between AD and RSV LRTI.
  • AD was associated with lower concentrations of basophils and plasmacytoid dendritic cells, increased NK-cells, and significantly lower TLR4-mediated IL-10 production.
  • RSV LRTI showed no association with neonatal immune cell counts or TLR-mediated cytokine production (TNF-α, IL-12p70, IL-10, IFN-α).

Conclusions:

  • Distinct pre-symptomatic differences in the innate immune system are associated with atopic dermatitis, but not with RSV LRTI.
  • A hypothesis is proposed suggesting that diminished neonatal IL-10-mediated immune regulation may play a causal role in initiating AD.
  • These findings highlight potential targets for early intervention in AD prevention.
Abstract

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