Infant home endotoxin is associated with reduced allergen-stimulated lymphocyte proliferation and IL-13 production in childhood
ABSTRACT Infant endotoxin exposure has been proposed as a factor that might protect against allergy and the early childhood immune responses that increase the risk of IgE production to allergens.
Using a prospective study design, we tested the hypothesis that early-life endotoxin exposure is associated with allergen- and mitogen-induced cytokine production and proliferative responses of PBMCs isolated from infants with a parental history of physician-diagnosed asthma or allergy.
We assessed household dust endotoxin at age 2 to 3 months and PBMC proliferative and cytokine responses to cockroach allergen (Bla g 2), dust mite allergen (Der f 1), cat allergen (Fel d 1), and the nonspecific mitogen PHA at age 2 to 3 years.
We found that increased endotoxin levels were associated with decreased IL-13 levels in response to cockroach, dust mite, and cat allergens, but not mitogen stimulation. Endotoxin levels were not correlated with allergen- or mitogen-induced IFN-gamma, TNF-alpha, or IL-10. Increased endotoxin levels were associated with decreased lymphocyte proliferation after cockroach allergen stimulation. An inverse, although nonsignificant, association was also found between endotoxin and proliferation to the other tested stimuli.
Increased early-life exposure to household endotoxin was associated with reduced allergen-induced production of the TH2 cytokine IL-13 and reduced lymphoproliferative responses at age 2 to 3 years in children at risk for allergy and asthma. Early-life endotoxin-related reduction of IL-13 production might represent one pathway through which increased endotoxin decreases the risk of allergic disease and allergy in later childhood.
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ABSTRACT: Background:We previously demonstrated that the proliferative response to lipopolysaccharide (LPS) in cord blood mononuclear cells (CBMC) is negatively correlated to the induced expression of interleukein (IL)-4. Our aim, therefore, was to examine whether an impaired cellular response to LPS in infancy, is associated with the risk for asthma.Methods:In a prospective cohort study, the relationship between the CBMC response to LPS and the risk of atopy and wheezing after the age of 4 years was evaluated.Results:LPS-induced CBMC proliferative responses varied markedly among the 102 infants studied (range, 1-5 fold increase over cells with diluent alone). Ninety-five infants (93%) were followed longitudinally. A higher CBMC proliferative response to LPS was noted in offspring born to non-atopic parents compared to those with at least one atopic parent (p=0.008). Using a proliferative index cutoff of 2 separated patients into high and low induced IL4 mRNA responders (p=0.001). Significantly more children who never wheezed had a greater than 2-fold LPS-induced CBMC proliferative response compared to those with persistent atopic wheezing (p=0.046).Conclusion:These results demonstrate that CBMC proliferative responses to LPS is impaired in infants born to atopic parents and may be a risk factor for asthma later in life.Pediatric Research (2013); doi:10.1038/pr.2013.74.Pediatric Research 05/2013; DOI:10.1038/pr.2013.74 · 2.84 Impact Factor
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ABSTRACT: IMPORTANCE The role of microbial exposure during early life in the development of type 1 diabetes mellitus is unclear. OBJECTIVE To investigate whether animal contact and other microbial exposures during infancy are associated with the development of preclinical and clinical type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS A birth cohort of children with HLA antigen-DQB1-conferred susceptibility to type 1 diabetes was examined. Participants included 3143 consecutively born children at 2 hospitals in Finland between 1996 and 2004. EXPOSURES The following exposures during the first year of life were assessed: indoor and outdoor dogs and cats, farm animals, farming, visit to a stable, day care, and exposure to antibiotics during the first week of life. MAIN OUTCOMES AND MEASURES Clinical and preclinical type 1 diabetes were used as outcomes. The latter was defined as repeated positivity for islet-cell antibodies plus for at least 1 of 3 other diabetes-associated autoantibodies analyzed and/or clinical type 1 diabetes. The autoantibodies were analyzed at 3- to 12-month intervals since the birth of the child. RESULTS Children exposed to an indoor dog, compared with otherwise similar children without an indoor dog exposure, had a reduced odds of developing preclinical type 1 diabetes (adjusted odds ratio [OR], 0.47; 95% CI, 0.28-0.80; P = .005) and clinical type 1 diabetes (adjusted OR, 0.40; 95% CI, 0.14-1.14; P = .08). All of the other microbial exposures studied were not associated with preclinical or clinical diabetes: the odds ratios ranged from 0.74 to 1.58. CONCLUSIONS AND RELEVANCE Among the 9 early microbial exposures studied, only the indoor dog exposure during the first year of life was inversely associated with the development of preclinical type 1 diabetes. This finding needs to be confirmed in other populations.JAMA Pediatrics 06/2014; 168(8). DOI:10.1001/jamapediatrics.2014.296 · 4.25 Impact Factor
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ABSTRACT: Previous studies have suggested that exposure to cats and dogs during early childhood reduces the risk of allergic disease, possibly by increasing home endotoxin exposure. This study asked the question of whether cats and dogs are the dominant influence on dust endotoxin concentrations in homes after considering other variables reportedly associated with endotoxin. The presence of cats or dogs in homes, household and home characteristics, and dust endotoxin concentrations from 5 locations were assessed in 966 urban and suburban homes. Whether considered together as pets or as cats and dogs separately, the presence of cats and dogs significantly contributed to living room and bedroom floor endotoxin concentrations but not to bed endotoxin concentrations. However, the two variables consistently related to endotoxin in all home sites were the home occupant density (occupants/room) and cleanliness of the home. Our data suggests that reducing occupant density and improving home cleanliness would reduce home endotoxin concentrations more than removing pet cats or dogs from the home. © 2012 John Wiley & Sons A/S.Indoor Air 11/2012; DOI:10.1111/ina.12016 · 4.20 Impact Factor