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Original Article
Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis
Article first published online: 20 SEP 2011
DOI: 10.1111/j.1365-2222.2011.03857.x
© 2011 Blackwell Publishing Ltd
1365-2222/asset/cover.gif?v=1&s=363d6ac7042b7535760df61b7393fd8e0a08e85f "Clinical & Experimental Allergy")
Additional Information
How to Cite
Publication History
- Issue published online: 27 DEC 2011
- Article first published online: 20 SEP 2011
- Manuscript Accepted: 18 JUL 2011
- Manuscript Revised: 17 JUL 2011
- Manuscript Received: 22 APR 2011
Funded by
- Netherlands Asthma Foundation. Grant Number: 3.2.07.001
- Alexandre Suerman foundation of the University Medical Center Utrecht
Keywords:
- allergic disease;
- atopy;
- bronchiolitis;
- endotoxin;
- hygiene hypothesis;
- newborn, eczema;
- Toll-like receptor
Summary
Background
Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are common diseases during early life. Impaired Th1-cell polarizing Toll-like receptor (TLR) responses play an important role in the pathogenesis of both diseases. Neonatal TLR-mediated production of Th1-type cytokines is decreased at birth, but rapidly increases during the first month of life.
Objective
To determine whether decreased TLR-mediated production of Th1-polarizing cytokines, at the age of 1 month is associated with subsequent AD or RSV LRTI.
Methods
A prospective healthy birth cohort study was performed. Whole blood concentrations of innate immune cells and TLR-mediated cytokine responses were measured at the age of 1 month in 291 neonates. AD was determined by a physician questionnaire at the age of 1 year and RSV LRTI was defined as parent-reported respiratory symptoms and presence of RSV RNA in a nose–throat specimen.
Results
Of participating neonates, 45 (15%) developed AD and 41 (14%) developed RSV LRTI. Risks of AD and RSV LRTI were not associated (χ2, P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 × 106/mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 × 106/mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 × 106/mL, P = 0.03), and twofold lower TLR4-mediated IL-10 production (P = 0.001). In contrast, RSV LRTI was associated neither with neonatal concentrations of innate immune cells, nor with TLR-mediated TNF-α, IL-12p70, IL-10 or IFN-αproduction.
Conclusions and Clinical Relevance
Atopic dermatitis, but not RSV LRTI, is associated with distinct pre-symptomatic differences in the innate immune system. We hypothesize that decreased neonatal IL-10-mediated immune regulation during early life might play a causal role in the initiation of AD.