暴露於低劑量鄰苯二甲酸鹽之小鼠免疫反應影響

前言：鄰苯二甲酸二酯（DEHP）是使用廣泛的環境干擾化學物質，具有干擾人體賀爾蒙作用的功能，流病調查顯示DEHP可能與氣喘以及一些過敏性疾病有關，但是其詳細機制目前並不清楚。目的：模擬人類暴露DEHP的方式與劑量，研究DEHP對小鼠樹突細胞之功能性影響。實驗方法：根據DEHP的每日可容許攝取量 (tolerable daily intake) 當做餵食的劑量 (37 ?慊/kg body weight/day)，利用管餵的方式使小鼠暴露於DEHP十天後，分析小鼠樹突細胞功能變化，並利用氣喘動物模式觀察DEHP的暴露對於小鼠氣喘肺部發炎情形的影響。結果：經由餵食DEHP十天之後，會使小鼠脾臟中樹突狀細胞 (cDC) 以及類漿細胞樹突狀細胞 (pDC) 的比例減少，且暴露於 DEHP的樹突狀細胞分泌IL-6的能力會增加，並且樹突狀細胞也會影響T細胞分化的能力，使得分泌IL-10細胞的比例減少。結論：DEHP的活體實驗顯示，DEHP會促進樹突細胞的發炎活性，並進一步減少抗發炎性T細胞的分化，因此DEHP可能可促使發炎性疾病的嚴重度增加。

關鍵字

鄰苯二甲酸二酯；樹突狀細胞

並列摘要

Introduction: Di (2-ethylhexyl) phthalate (DEHP) is widely used environment disrupting chemicals that can interfere with human hormones function. Previous epidemiological studies have shown that DEHP exposure is associated with the prevalence of human asthma and other allergic diseases; however, the detailed mechanism is not clear. Specific aim: We aimed to examine the functional impact of DEHP on dendritic cells in vivo. Methods: In order to simulate the human exposure way, BALB/c mice were orally fed 37 ?慊 DEHP/kg body weight/day based on human tolerable daily intake for 10 days. Purified splenic DCs were analyzed for cytokine pattern, maturity and T-cell differentiated activity. We also tested the effect of DEHP exposure on the lung inflammation in OVA-induced asthma model. Results: After 10-day DEHP exposure, the frequencies of splenic conventional DCs and plasmacytoid DCs were significantly decreased. Splenic DCs from DEHP-exposed mice were expressed more proinflammatory cytokine, IL-6 in response to CpG than those from control mice. DEHP-exposed DCs also differentiated less IL-10-secreting CD4+ T cells from naïve T cells compared with control DCs. Conclusion: Our in vivo data suggest that DEHP may promote inflammatory activity by increasing proinflammatoy cytokine production and decreasing anti-inflammatory T cell differentiation. It suggests DEHP may enhance the severity of inflammatory diseases.

並列關鍵字

DEHP ； dendritic cells

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