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

被引:24
作者
Belderbos, M. E. [1 ]
Knol, E. F. [2 ]
Houben, M. L. [1 ]
van Bleek, G. M. [1 ]
Wilbrink, B. [3 ]
Kimpen, J. L. L. [1 ]
Rovers, M. [4 ]
Bont, L. [1 ]
机构
[1] Univ Med Ctr Utrecht, Dept Pediat, Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Dept Dermatol & Allergol, Utrecht, Netherlands
[3] Natl Inst Publ Hlth & Environm, Lab Infect Dis & Perinatal Screening, NL-3720 BA Bilthoven, Netherlands
[4] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands
关键词
allergic disease; atopy; bronchiolitis; endotoxin; hygiene hypothesis; newborn; eczema; Toll-like receptor; HOUSE-DUST ENDOTOXIN; SYNCYTIAL VIRUS-INFECTION; INNATE IMMUNITY; HIGH-RISK; ALLERGEN; SENSITIZATION; RESPONSES; CHILDREN; EXPRESSION; MONOCYTES;
D O I
10.1111/j.1365-2222.2011.03857.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 (v2, P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 9 10 6/mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 9 10 6/mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 9 10 6/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-a, IL-12p70, IL-10 or IFN-a production. 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.
引用
收藏
页码:66 / 75
页数:10
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