Analysis of modification of allergic responses observed in formaldehyde exposed mice

将小鼠暴露于500 ppb甲醛（HCHO）中，每天8小时，每周6天，持续6周。分别以偏苯三酸（TMA）和卵清蛋白（OVA）作为I型变态反应的致敏原，以恶唑酮（OXZ）作为IV型变态反应的致敏原，诱导每种类型的变态反应。使用TMA或OXZ进行局部淋巴结测定（LLNA）以评价致敏相。为了评价出现的阶段，采用以下方法。卵清蛋白（OVA）在腹腔或鼻腔内重复处理，以评价IgE的产生。致敏后第5天将OXZ涂于耳背，观察耳组织厚度、组织学及mRNA表达情况，评价迟发型变态反应。在含TMA的LLNA中，主要观察到暴露小鼠的细胞数量增加和细胞增殖增强。在对照组和暴露组小鼠中观察到相同水平的LLNA与OXZ。在暴露小鼠中，ip致敏后抗OVA IgE滴度略有升高，但鼻腔致敏后显著降低。与对照组小鼠相比，暴露组小鼠出现早期耳肿胀高峰。在组织学观察中，暴露组小鼠耳部炎性细胞浸润程度较低，水肿较重，而对照组小鼠耳部炎性细胞浸润程度较高，水肿程度较轻。暴露组小鼠耳组织中与IV型变态反应相关的细胞因子mRNA表达受到抑制，而与I型变态反应相关的细胞因子mRNA表达无明显变化。我们的数据表明，甲醛调节过敏反应;甲醛暴露可能会加速I型过敏和中度IV型过敏的两个阶段的致敏和过敏症状的出现。这些发现意味着甲醛加速过敏性疾病的致敏和症状。

Mice were exposed to 500ppb formaldehyde (HCHO) daily 8 hr, 6 days in week for 6 weeks. Trimelitic acid (TMA) and oval albumin (OVA) for type I allergy, and oxazolone (OXZ) for type IV allergy were employed as allergens to induce each type of allergic responses. Local lymph node assay (LLNA) were performed using TMA or OXZ for evaluation of the sensitizing phase. For evaluation of the arising phases, followed methods were employed. Oval albumin (OVA) was treated repeatedly inter peritonea cavity (ip) or nasal cavities, for evaluation of IgE production. OXZ were painted on back of ear at day 5 after the sensitization and observed thickness, histology and mRNA expression in ear for evaluation of delayd type allergic response. In LLNA with TMA,increase of cell number and enhancement of cell proliferation were observed dominantly in exposed mice. LLNA with OXZ,those were observed equal level in control and exposed mice. Anti-OVA IgE titer elevated slightly with ip sensitization but strongly reduced with nasal cavities sensitization in exposed mice. Exposed mice showed early peak of ear swelling compare control mice. In histological observation, exposed mice ear showed low infiltration of inflammatory cells and sever edema, although high cell infiltration and moderate edema in control mice. Expression of type IV allergy relating cytokine mRNA was suppressed in ear tissues of exposed group, but that of type I allergy was unchanged. Our data suggest that HCHO modulates allergic responses ; HCHO exposure may accelerate type I allergy and moderate type IV allergy in both phases of sensitization and arising of allergy symptoms. Those findings mean HCHO accelerates sensitization and symptoms of atopic diseases.