BackgroundIn early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such as animal dander or tree and grass pollen. MethodsParents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children. ResultsEndotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor a , interferong , interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children.Conclusions A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments. (N Engl

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Possible explanations for the lower prevalence of hay fever, asthma and allergic sensitization in children living on a farm might be the development of immunotolerance or the stimulation of TH1 cells and suppression of TH2 cells by increased exposure of farm children to microbial antigens in the stables or farmhouses.

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