| Budget Amount *help |
¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥3,200,000 (Direct Cost: ¥3,200,000)
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| Research Abstract |
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.
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