Relation between house-dust endotoxin exposure, type 1 T cell development, and allergen sensitisation in infants at high risk of asthma

Relation between house-dust endotoxin exposure, type 1 T cell development, and allergen sensitisation in infants at high risk of asthma
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DOI:
10.1016/s0140-6736(00)02239-x
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发表时间:
2000-05-13
期刊:
影响因子:
168.9
通讯作者:
Liu, AH
Liu, AH
中科院分区:
医学1区
文献类型:
--
作者:
Gereda, JE;Leung, DYM;Liu, AH

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背景已知细菌内毒素可诱导干扰素 γ 和白细胞介素 12 的产生,因此具有降低过敏原致敏的潜力。为了找出早期慢性内毒素暴露在过敏原致敏和哮喘发展中的作用,我们将室内灰尘中的内毒素浓度与哮喘高危婴儿的过敏原致敏进行了比较。方法 61 名 9-24 个月大的哮喘婴儿。研究了至少三起医生记录的喘息发作。在婴儿家里测量了室内灰尘内毒素和过敏原的浓度。过敏原致敏性是通过一组常见吸入剂和食物过敏原的皮肤点刺测试来测量的。在这些婴儿的一个子集中,通过细胞表面和细胞内细胞因子染色和流式细胞术计算产生干扰素 γ 以及白细胞介素 4、5 和 13 的 T 淋巴细胞的比例。结果发现室内灰尘内毒素浓度范围为每吨 104 至 10 000 内毒素单位 (EU)(几何平均值 912 EU/mL)。在 6 个月的时间间隔内,浓度没有显着变化。十名婴儿 (16%) 对至少一种过敏原过敏。过敏原敏感婴儿的家中灰尘内毒素浓度显着低于非过敏婴儿的家中(平均值分别为 468 EU/mL 和 1035 EU/mL;p=0.01)。室内灰尘内毒素浓度的增加与产生干扰素 γ 的 CD4 T 细胞比例的增加相关 (p=0.01)。这样的浓度与产生白介素 4、5 或 13 的细胞比例无关。 解释 这项研究可能提供第一个直接的体内证据,证明生命早期的室内内毒素暴露可以通过增强 1 型免疫力来防止过敏原致敏。
Background Bacterial endotoxin is known to induce interferon gamma and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma.Methods 61 infants 9-24 months old with at. least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry.Findings House-dust endotoxin concentrations ranged from 104 to 10 000 endotoxin units (EU) per mt (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-gamma-producing CD4 T cells (p=0.01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13.Interpretation This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.