Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide.
Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide.
复制标题
局部应用第四纪铵化合物Docyldimethylamonium溴化物后，发散的超敏反应。
DOI：
10.1080/1547691x.2017.1397826
复制
发表时间：
2017-12
影响因子：
3.3
通讯作者：
Anderson SE
中科院分区：
文献类型：
--
作者：
Shane HL;Lukomska E;Stefaniak AB;Anderson SE
二烷基二甲基溴化铵(DDAB)是第四代二烷基季铵化合物(QAC)，因其抗菌性能而被广泛应用于多种产品中。虽然许多QAC与过敏性疾病有关，但DDAB的毒性和致敏作用尚未得到彻底研究。这些研究的目的是评估DDAB在小鼠皮肤应用后的刺激性和致敏潜力。DDAB对雌性BALB/c小鼠有明显的刺激性(0.0625-2%)，以耳肿胀为评价指标。在浓度从0.0625%到2%的范围内，使用局部淋巴结检验法对致敏潜力进行初步评估。淋巴细胞增殖呈浓度依赖性增加，计算的EC3值为0.057%。在4天和14天的皮肤涂抹后，评估免疫细胞表型以及局部和系统的IgE水平。表型分析显示，皮肤暴露4天和14天后，引流淋巴结(DLN)中B细胞、CD4+T细胞、CD8+T细胞和树突状细胞的绝对数显著增加，并呈剂量反应关系，活化的B细胞和树突状细胞的数量显著增加。然而，只有在接触DDAB四天后，才能观察到CD4+T细胞和CD8+T细胞的激活增加。暴露于DDAB后，通过对DLN B细胞(IgE+B细胞)的表型分析和14天(而不是4天)皮下注射后血清总IgE水平的测定，也可以诱导IgE的产生增加。在DDAB暴露4天和14天后，DLN(IL-4、IL-10和ox401)和EAR(TSLP)的基因表达显著增加。这些结果表明，皮肤暴露后可能对DDAB产生刺激性和超敏反应，并引起了人们对暴露时间对超敏反应影响的关注。
Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625–2%), evaluated by ear swelling in female BALB/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. Phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells, and dendritic cells in the draining lymph nodes (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4+ T-cell and CD8+ T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE+ B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.