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Maternal allergy influences p38-mitogen-activated protein kinase activity upon microbial challenge in CD14+ monocytes from 2-year-old children
Authors:S. Saghafian-Hedengren,U. Holmlund,P. Amoudruz,C. Nilsson, E. Sverremark-Ekströ  m
Affiliation:Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden and;Department of Pediatrics, Sachs' Children's Hospital, Karolinska Institute, Stockholm, Sweden
Abstract:Background The development of allergic diseases is dependent on genetic and environmental factors. It has been shown previously that cord blood mononuclear cells (CBMCs) from infants with parental allergy have altered cytokine profiles upon bacterial encounter; it might be possible that such impairment persists during the early years of childhood. Objective The aim of this study was to investigate anti‐microbial responses with regard to p38‐mitogen‐activated protein kinase (MAPK) activity in CD14+ monocytes and IL‐6 release from mononuclear cells in the same group of children at birth and at 2 years of age. Methods Paired samples of CBMCs and peripheral blood mononuclear cells (PBMCs) were stimulated with either lipopolysaccharide (LPS) or peptidoglycan in vitro. CD14+ monocytes were analysed for p38‐MAPK activity by flow cytometry, and soluble IL‐6 receptor, soluble glycoprotein130 and IL‐6 release from PBMC cultures were quantified by ELISA. Results CBMCs from newborns with allergic mothers tended to have a lower IL‐6 response following an LPS (P=0.09) challenge compared with the group without maternal allergy while p38‐MAPK activation levels did not differ between the groups. PBMCs from 2‐year‐olds with allergic mothers released significantly less (P<0.05) IL‐6 upon peptidoglycan stimuli compared with age‐matched infants with non‐allergic mothers. Infants with allergic mothers displayed markedly reduced CD14+ monocyte p38‐MAPK phosphorylation after LPS (P<0.05) and peptidoglycan (P<0.01) challenge. This altered anti‐microbial response was attributed to maternal allergy rather than to being IgE‐sensitized at 2 years of age. Conclusion Monocytes from children with allergic mothers are less responsive to bacterial challenge than monocytes from children with non‐allergic mothers, and this impairment persists during the first 2 years of infancy.
Keywords:CD14+ monocytes    IL-6    maternal allergy    microbial stimuli    p38-MAPK
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