Gerhold Kerstin, Bluemchen Katharina, Franke Annabelle, Stock Philippe, Hamelmann Eckard
Department of Pediatric Pneumology and Immunology, University Hospital Charité, Berlin, Germany.
J Allergy Clin Immunol. 2003 Aug;112(2):389-96. doi: 10.1067/mai.2003.1646.
Exposure to endotoxins, allergens, or both in early life might regulate the development of tolerance to allergens later in life.
We investigated whether continuous exposure of infant mice to aerosolized endotoxin, allergen, or both inhibits subsequent allergen-induced immune and inflammatory responses.
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.
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/microL; eosinophils, 28 +/- 5 vs 1 +/- 0/microL) 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.
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.
生命早期接触内毒素、过敏原或两者可能会调节后期对过敏原耐受性的发展。
我们研究了幼鼠持续暴露于雾化内毒素、过敏原或两者是否会抑制随后过敏原诱导的免疫和炎症反应。
在全身致敏（第1 - 14天）和用卵清蛋白（OVA）进行重复气道激发（第28 - 30天）之前，将幼龄BALB/c小鼠预先暴露于雾化内毒素、OVA或两者（出生后的前4周每周3次）。
与阴性对照动物相比，全身致敏和气道过敏原激发诱导了高血清水平的过敏原特异性IgE（0.7±0.09对0.02±0.01 OD单位）、主要的Th2型细胞因子产生（体外脾单核细胞产生的IL - 5，1.2±0.2对0.04±0.06 ng/mL）、气道炎症（支气管肺泡灌洗液白细胞，125±15对64±7/μL；嗜酸性粒细胞，28±5对1±0/μL）以及体内气道高反应性的发展（最大增强呼吸暂停，11±1.9对4±0.2）。致敏前用脂多糖预先暴露增加了特异性IgG2a的产生（67±10对32±5 U/mL），但未能预防Th2介导的免疫反应。用OVA或OVA加LPS预先暴露完全抑制了过敏原致敏、气道炎症和体内气道高反应性的发展；数值与阴性对照动物相似。抑制是由于省略的过敏原特异性Th2和Th1免疫反应所表明的过敏原特异性T细胞无反应性。此外，内毒素和过敏原的联合暴露诱导了向非特异性Th1免疫反应的总体转变。
在过敏原致敏前接触内毒素不能诱导无反应性，但可能会降低对多种常见过敏原致敏的易感性。
