Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland.
J Dermatol Sci. 2010 Jun;58(3):186-92. doi: 10.1016/j.jdermsci.2010.03.011. Epub 2010 Mar 23.
The market release of new domestic and industrial chemical and metal products requires certain safety certification, including testing for skin sensitisation. Although various official guidelines have described how such testing is to be done, the validity of the available test models are in part dubious, for which reason regulatory agencies and research aim to further improve and generalise the models for testing of skin sensitisation.
We applied a recently published murine model of nickel allergy as to test its applicability in a regulatory setting and to study and better understand the events leading to type-IV hypersensitivity. Nickel was chosen as model hapten since it induces allergic contact dermatitis with high incidence in the general population.
Typically, C57BL/6 mice were sensitised and challenged by intradermal applications of nickel, and cutaneous inflammation was analysed by the mouse ear-swelling test, by histology, and by lymphocyte reactivity in vitro.
Surprisingly, the study suggested that the skin reactions observed were results of irritant reactions rather than of adaptive immune responses. Non-sensitised mice responded with cutaneous inflammation and in vitro lymphocyte reactivity which were comparable with nickel-sensitised mice. Furthermore, histological examinations as well as experiments in T-cell deficient mice demonstrated that lymphocytes were not involved and that nickel caused an irritant contact dermatitis rather a true allergic type-IV contact dermatitis.
The authors question the validity of the described murine model of nickel allergy.
新的国产和工业化学及金属产品投放市场需要进行一定的安全认证,包括皮肤致敏测试。尽管各种官方指南都描述了如何进行此类测试,但现有的测试模型的有效性在一定程度上是值得怀疑的,因此监管机构和研究人员旨在进一步改进和推广用于皮肤致敏测试的模型。
我们应用了最近发表的镍过敏的啮齿动物模型,以测试其在监管环境中的适用性,并研究和更好地了解导致 IV 型超敏反应的事件。镍被选为模型半抗原,因为它在普通人群中引起高发生率的过敏性接触性皮炎。
通常,C57BL/6 小鼠通过皮内应用镍进行致敏和挑战,并通过小鼠耳肿胀试验、组织学和体外淋巴细胞反应性来分析皮肤炎症。
令人惊讶的是,该研究表明观察到的皮肤反应是刺激性反应的结果,而不是适应性免疫反应的结果。未致敏的小鼠表现出与镍致敏的小鼠相当的皮肤炎症和体外淋巴细胞反应性。此外,组织学检查以及 T 细胞缺陷小鼠的实验表明,淋巴细胞未参与其中,镍引起刺激性接触性皮炎,而不是真正的 IV 型过敏性接触性皮炎。
作者对所描述的镍过敏啮齿动物模型的有效性提出了质疑。