Exposure to endotoxin and allergen in early life and its effect on allergen sensitization in mice
Exposure to endotoxin and allergen in early life and its effect on allergen sensitization in mice
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DOI：
10.1067/mai.2003.1646
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发表时间：
2003-08-01
影响因子：
14.2
通讯作者：
Hamelmann, E
中科院分区：
文献类型：
--
作者：
Gerhold, K;Bluemchen, K;Hamelmann, E
背景资料：暴露于内毒素，过敏原，或两者在生命早期可能会调节发展的耐受性过敏原在以后的life.Objective：我们调查是否持续暴露的婴儿小鼠雾化内毒素，过敏原，或两者抑制随后过敏原诱导的免疫和炎症反应。将婴儿BALB/c小鼠预先暴露于雾化的内毒素、卵清蛋白（OVA），或两者全身致敏前（出生后前4周每周3次）（第1-14天）和重复气道激发（第28-30天）。与阴性对照动物相比，全身致敏和气道变应原激发诱导高血清变应原特异性IgE水平（0.7 +/- 0.09 vs 0.02 +/- 0.01 OD单位），主要T（H）2型细胞因子产生（体外脾单核细胞IL-5，1.2 +/- 0.2 vs 0.04 +/- 0.06 ng/mL），气道炎症（支气管肺泡灌洗液白细胞，125 +/- 15 vs 64 +/- 7/穆尔;嗜酸性粒细胞，28 +/- 5 vs 1 +/- 0/穆尔）和体内气道高反应性的发展（最大增强暂停，11 +/- 1.9 vs 4 +/- 0.2）。致敏前用LPS预暴露可增加特异性IgG 2a的产生（67 +/- 10 vs 32 +/- 5 U/mL），但未能阻止T（H）2介导的免疫应答。用OVA或用OVA加LPS预暴露完全抑制过敏原致敏、气道炎症和体内气道高反应性的发展;值与阴性对照动物的值相似。抑制是由于过敏原特异性T细胞无反应性，由省略的过敏原特异性T（H）2和T（H）1免疫应答指示。此外，联合暴露于内毒素和过敏原诱导的一般转向非特异性T（H）1 immune responsibility.Conclusion：暴露与内毒素过敏原致敏前不能诱导无反应性，但可能会降低各种常见过敏原致敏的易感性。
Background: Exposure to endotoxins, allergens, or both in early life might regulate the development of tolerance to allergens later in life.Objective: We investigated whether continuous exposure of infant mice to aerosolized endotoxin, allergen, or both inhibits subsequent allergen-induced immune and inflammatory responses.Methods: Infant BALB/c mice were pre-exposed to aerosolized endotoxin, ovalbumin (OVA), or both (3 times a week for the first 4 weeks of life) before systemic sensitization (days 1-14) and repeated airway challenge (days 28-30) with OVA.Results: Compared with that seen in negative control animals, systemic sensitization and airway allergen challenges induced high serum levels of allergen-specific IgE (0.7 +/- 0.09 vs 0.02 +/- 0.01 OD units), predominant T(H)2-type cytokine production (IL-5 by splenic mononuclear cells in vitro, 1.2 +/- 0.2 vs 0.04 +/- 0.06 ng/mL), airway inflammation (bronchoalveolar lavage fluid leukocytes, 125 +/- 15 vs 64 +/- 7/muL; eosinophils, 28 +/- 5 vs 1 +/- 0/muL) and development of in vivo airway hyperreactivity (maximal enhanced pause, 11 +/- 1.9 vs 4 +/- 0.2). Pre-exposure with LPS before sensitization increased production of specific IgG2a (67 +/- 10 vs 32 +/- 5 U/mL) but failed to prevent T(H)2-mediated immune responses. Pre-exposure with OVA or with OVA plus LPS completely suppressed allergen sensitization, airway inflammation, and development of in vivo airway hyperreactivity; values were similar to those of negative control animals. Inhibition was due to allergen-specific T-cell anergy indicated by omitted allergen-specific T(H)2 and T(H)1 immune responses. In addition, combined exposure to endotoxin and allergen induced a general shift toward an unspecific T(H)1 immune response.Conclusion: Exposure with endotoxins before allergen sensitization is not able to induce unresponsiveness but might decrease the susceptibility for sensitization to a variety of common allergens.