Smart J M, Tang M L K, Kemp A S
Department of Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Australia.
Clin Exp Allergy. 2002 Nov;32(11):1552-7. doi: 10.1046/j.1365-2222.2002.01532.x.
Reduced Th1 and elevated Th2 cytokine responses are considered to be a principal mechanism in the generation of the inflammation leading to the manifestations of atopic disease in the skin of atopic dermatitis and in the airways of asthma. If reduced Th1 and elevated Th2 responses are principal determinants of the manifestation of atopic disease it might be expected that subjects with established disease would exhibit differences in their cytokine profiles as compared with atopic patients without clinical disease.
To determine whether asymptomatic atopic children exhibit a cytokine imbalance similar to that seen in patients with established atopic disease or if they behave like non-atopic controls. Cytokine responses in a group of children with elevated IgE but no clinical manifestations of disease, atopic children with established disease and non-atopic controls were compared.
We examined allergen-induced (house dust mite, HDM, rye grass pollen and RYE) cytokine responses in parallel with polyclonal (staphylococcal enterotoxin B, SEB) cytokine responses in a group of children with elevated serum IgE levels without current or past evidence of atopic disease (median age 6.6 years) and compared these with a non-atopic control group (median age 6.5 years) and a group of children with atopic disease (median age 6.7 years).
Symptomatic atopic children had reduced SEB-induced IFN-gamma and increased SEB-induced IL-4 and IL-5 as compared with non-atopic controls. In contrast, SEB-induced IFN-gamma, IL-4 and IL-5 production in asymptomatic atopics was not significantly different from the non-atopic control subjects. Allergen-induced Th1 (IFN-gamma) and Th2 (IL-5 and IL-13) cytokine production was increased in both symptomatic atopics and asymptomatic atopics when compared with non-atopic controls.
The defect in polyclonally induced IFN-gamma production was associated with the clinical manifestation of atopic disease but not the atopic stateper se. This suggests that the global reduction in IFN-gamma is the key determinant of the development of overt atopic disease. In contrast, elevated allergen-induced Th2 cytokine responses in children related to the atopic state per se irrespective of the presence of clinical atopic disease.
Th1反应降低和Th2细胞因子反应升高被认为是导致特应性皮炎皮肤和哮喘气道中特应性疾病表现的炎症产生的主要机制。如果Th1反应降低和Th2反应升高是特应性疾病表现的主要决定因素，那么可以预期，与无临床疾病的特应性患者相比，患有已确诊疾病的受试者在细胞因子谱上会表现出差异。
确定无症状特应性儿童是否表现出与已确诊特应性疾病患者相似的细胞因子失衡，或者他们的表现是否与非特应性对照相似。比较了一组IgE升高但无疾病临床表现的儿童、已确诊疾病的特应性儿童和非特应性对照的细胞因子反应。
我们检测了一组血清IgE水平升高但目前或既往无特应性疾病证据的儿童（中位年龄6.6岁）对变应原（屋尘螨、HDM、黑麦草花粉和RYE）诱导的细胞因子反应以及多克隆（葡萄球菌肠毒素B，SEB）诱导的细胞因子反应，并将这些反应与非特应性对照组（中位年龄6.5岁）和一组患有特应性疾病的儿童（中位年龄6.7岁）进行比较。
与非特应性对照相比，有症状的特应性儿童SEB诱导的IFN-γ降低，SEB诱导的IL-4和IL-5升高。相比之下，无症状特应性个体中SEB诱导的IFN-γ、IL-4和IL-5产生与非特应性对照受试者无显著差异。与非特应性对照相比，有症状的特应性个体和无症状的特应性个体中变应原诱导的Th1（IFN-γ）和Th2（IL-5和IL-13）细胞因子产生均增加。
多克隆诱导的IFN-γ产生缺陷与特应性疾病的临床表现相关，但与特应性状态本身无关。这表明IFN-γ的整体降低是明显特应性疾病发展的关键决定因素。相比之下，与特应性状态本身相关的儿童变应原诱导的Th2细胞因子反应升高，而与临床特应性疾病的存在无关。
