Evaluation of immunotoxicity of occupational chemicals based on cytokine analysis

在这项研究中，我们已经评估了职业化学品的免疫毒性，特别是职业致敏剂通过分析各种细胞因子的活动和它们的基因表达。首先，我们用定量RT-PCR检测了用强接触致敏剂如DNCB、恶唑酮和苦酰氯致敏的小鼠引流淋巴结中的9种细胞因子mRNA。观察到在接触过敏后6天，引流淋巴结中Th 1（IL-2、IL-12和IFN-γ）和Th 2细胞因子mRNA（IL-4、IL-10和IL-13）均显著升高，表明接触致敏剂诱导了Th 1和Th 2细胞因子基因。同时，在DNCB、恶唑酮和苦氯的接触性变态反应性皮炎小鼠皮损中，IL-2、IL-4、IL-12和IFN-γ mRNA表达上调。此外，为了证实上述发现是否对所有接触致敏剂都是共同的，我们检查了福尔马林致敏小鼠引流淋巴结和炎症皮肤中的细胞因子mRNA。我们发现，IL-2，IL-4，IL-12，IL-13和IFN-γ mRNA的表达在最后一次应用福尔马林后三天在淋巴结中显著增强。在皮肤损伤的情况下，IL-4和IFN-γ mRNA均显著高于对照小鼠。皮肤部位的细胞因子mRNA与小鼠耳肿胀反应测量的接触性超敏反应呈正相关。此外，我们还测试了重组IL-12是否可以在预测试验中用作佐剂。结果表明，IL-12通过促进体内Th 1细胞因子和抑制体内Th 2细胞因子显着增强接触性超敏反应。两者合计，这项研究表明，有用的细胞因子分析职业化学品的免疫毒性评价。

In this study, we have evaluated the immunotoxicity of occupational chemicals, in particular occupational sensitizers by analyzing various cytokine activities and their gene expression. Firstly, using quantitative RT-PCR we have detected nine cytokine mRNAs in the draining lymph nodes of mice sensitized with strong contact sensitizers such as DNCB,oxazolone and picryl chloride. It was observed that both Th1 (IL-2, IL-12 and IFN-gamma) and Th2 cytokine mRNAs (IL-4, IL-10 and IL-13) were significantly elevated in the draining lymph nodes 6 days following contact sensitivity, indicating the induction of both Th1 and Th2 cytokine genes by contact sensitizers. Meanwhile, the up-regulated expression of IL-2, IL-4, IL-12 and IFN-gamma mRNAs was further demonstrated in the skin lesions of mice with contact allergic dermatitis to DNCB,oxazolone and picryl chloride. Moreover, to confirm wether the above findings are common to all contact sensitizers we have examined the cytokine mRNAs in the draining lymph nodes and inflammatory skin in formalin-sensitized mice. We found that the expression of IL-2, IL-4, IL-12, IL-13 and IFN-gamma mRNAs was markedly enhanced in the lymph nodes three days after the last application of formalin. In the case of the skin lesions, both IL-4 and IFN-gamma mRNAs were significantly higher than those in control mice. The cytokine mRNAs at the skin sites were positively correlated with contact hypersensitivity as measured by mouse ear swelling response. Furthermore, we have tested if recombinant IL-12 could be used as adjuvant in the predicting tests. As results, we have demonstrated that IL-12 significantly enhanced contact hypersensitivity by promoting Th1 cytokines and suppressing Th2 cytokines in vivo. Taken together, this study indicates the usefulness of cytokine analysis in the evaluation of immunotoxicity from occupational chemicals.