Braun-Fahrländer Charlotte, Riedler Josef, Herz Udo, Eder Waltraud, Waser Marco, Grize Leticia, Maisch Soyoun, Carr David, Gerlach Florian, Bufe Albrecht, Lauener Roger P, Schierl Rudolf, Renz Harald, Nowak Dennis, von Mutius Erika
Institute of Social and Preventive Medicine, Basel, Switzerland.
N Engl J Med. 2002 Sep 19;347(12):869-77. doi: 10.1056/NEJMoa020057.
In 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.
Parents 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.
Endotoxin 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 alpha, interferon-gamma, 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.
A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.
在生命早期，先天性免疫系统能够识别微生物的活的和非活的部分。免疫激活可引导免疫反应，从而赋予对诸如动物皮屑或树木及草花粉等过敏原的耐受性。
居住在德国、奥地利或瑞士农村地区的6至13岁儿童的父母，这些地区既有农户家庭也有非农户家庭，他们完成了一份关于哮喘和花粉热的标准化问卷。采集这些儿童的血样并检测特应性致敏情况；还从血样中采集外周血白细胞进行检测。检测这些儿童使用的床上用品中的内毒素水平，并将其与临床结果以及用脂多糖和葡萄球菌肠毒素B刺激后的外周血白细胞的细胞因子产生谱进行关联分析。共有812名儿童获得了完整数据。
儿童床垫灰尘样本中的内毒素水平与花粉热、特应性哮喘和特应性致敏的发生呈负相关。非特应性喘息与内毒素水平无显著关联。白细胞产生的细胞因子（肿瘤坏死因子α、干扰素-γ、白细胞介素-10和白细胞介素-12的产生）与床上用品中的内毒素水平呈负相关，表明暴露儿童的免疫反应明显下调。
个体环境中内毒素暴露可能在对自然环境中普遍存在的过敏原产生耐受性方面起关键作用。
