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Low neonatal T oll‐like receptor 4‐mediated interleukin‐10 production is associated with subsequent atopic dermatitis
Author(s) -
Belderbos M. E.,
Knol E. F.,
Houben M. L.,
Bleek G. M.,
Wilbrink B.,
Kimpen J. L. L.,
Rovers M.,
Bont L.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2011.03857.x
Subject(s) - medicine , immunology , atopic dermatitis , lower respiratory tract infection , immune system , respiratory system , cytokine , innate immune system , asthma , allergy , respiratory tract , toll like receptor , respiratory tract infections
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 T oll‐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 (χ 2 , P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 × 10 6 / mL , P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 × 10 6 / mL , P = 0.04), increased concentrations of NK ‐cells (79.7 vs. 45.1 × 10 6 / mL , P = 0.03), and twofold lower TLR 4‐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 .