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Early onset wheeze associated with enhanced combined IL‐1β, IL‐6, and IL‐12/IL‐23p40 in LPS‐stimulated cord blood mononuclear cells
Author(s) -
Quah P. L.,
Kuo IC,
Huang C. H.,
Shek L. PC,
Lee B. W.,
Chua K. Y.
Publication year - 2011
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.1365-2222.2011.03760.x
Subject(s) - wheeze , medicine , cord blood , immunology , atopy , peripheral blood mononuclear cell , asthma , allergy , umbilical cord , cytokine , biology , biochemistry , in vitro
Summary Background Neonates with a family history of atopy are at higher risk for developing wheezing in early life. Objective From a birth cohort of at risk infants (first‐degree family with atopic disease), we evaluated the influence of distinct intrinsic immunologic risk factors on wheezing disorders in the first 2 years of life. Methods Cord blood samples were collected from 195 eligible subjects of a birth cohort of 253 subjects. The subjects studied were those who developed wheezing ( n =34) or eczema ( n =29) in the first 2 years of life, and 65 healthy control infants. At the time of thawing the viability of the cells were median 70% (range 67.5%–72.5%). Cytokines from lipopolysaccharide (LPS)‐stimulated mononuclear cells were analysed using fluorescent‐activated cell sorting‐array and their profiles were evaluated using factor analysis. Results Infants with wheeze were significantly associated with enhanced combined LPS stimulated IL‐1β, IL‐6, and IL‐12/IL‐23p40 compared with healthy controls ( P =0.003). This profile was also associated with the increased risk for wheeze at 2 years of age (OR=2.45; 95% CI=1.50–3.93, P =0.001). LPS‐stimulated cytokine IL‐8 was also significantly higher in the wheeze group compared with healthy controls and eczema ( P =0.003). Intracellular staining showed that monocytes are main producers of IL‐6 and IL‐8 from cord blood mononuclear cells. Most of the subjects were non‐atopic with 3/34 (9%) wheeze and 9/29 (31%) eczema subjects sensitized to the common dietary or inhalant allergens. Conclusion and Clinical Relevance In infants at genetic risk of atopy, wheeze but not eczema in the first 2 years of life is associated with intrinsic hyperresponsive innate cytokine responses which might predispose infants to wheeze development. Distinct pre‐symptomatic hyperresponsive innate immune responses risk factors were found to be associated with early onset wheeze disorders, but not eczema. Cite this as : P. L. Quah, I‐C Kuo, C. H. Huang, L. P‐C Shek, B. W. Lee and K. Y. Chua, Clinical & Experimental Allergy , 2011 (41) 970–978.