Kimber Ian, Basketter David A, Gerberick G Frank, Dearman Rebecca J
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.
Int Immunopharmacol. 2002 Feb;2(2-3):201-11. doi: 10.1016/s1567-5769(01)00173-4.
Allergic contact dermatitis (ACD) is a common occupational and environmental health issue. In common with other forms of allergy the disease progresses in two stages; an initial phase during which sensitization is acquired, followed later (after subsequent exposure to the same chemical allergen) by elicitation of a cutaneous inflammatory reaction. The development of skin sensitization is associated with, and requires, the activation and clonal expansion of allergen responsive T lymphocytes and it is these cells that orchestrate the cutaneous allergic reaction. In recent years, much has been learned of the characteristics of immune responses to skin sensitizing chemicals and of the roles played by dendritic cells, cytokines and chemokines. Some of the more interesting cellular and molecular mechanisms are reviewed briefly in this article. A more detailed appreciation of responses induced by chemical allergens has in turn facilitated the design of novel approaches to the toxicological evaluation of skin sensitization. Real progress has been made, not only in the development of improved methods for hazard identification and characterization, but also in the application of new paradigms for risk assessment. The newer methods now available and the opportunities that exist for further advances are considered. Finally, progress has been made in the characterization of skin sensitization in humans and in the clinical management of ACD. This article seeks to consider skin sensitization and ACD in holistic fashion, bridging experimental observations with clinical disease and basic mechanisms with practical toxicology.
过敏性接触性皮炎（ACD）是一个常见的职业与环境卫生问题。与其他形式的过敏一样，该病分两个阶段发展：第一阶段为致敏阶段，在此期间机体获得致敏；随后（在再次接触相同化学变应原后）进入激发阶段，引发皮肤炎症反应。皮肤致敏的发生与变应原反应性T淋巴细胞的激活和克隆扩增相关且依赖于此，正是这些细胞协调了皮肤过敏反应。近年来，我们对皮肤致敏化学物质的免疫反应特征以及树突状细胞、细胞因子和趋化因子所起的作用有了很多了解。本文简要综述了一些较为有趣的细胞和分子机制。对化学变应原诱导的反应有了更深入的认识，反过来又促进了皮肤致敏毒理学评价新方法的设计。不仅在改进危害识别和表征方法的开发方面取得了实际进展，而且在应用新的风险评估范式方面也取得了进展。本文将探讨现有的较新方法以及进一步取得进展的机会。最后，在人类皮肤致敏的表征和ACD的临床管理方面也取得了进展。本文旨在以整体的方式探讨皮肤致敏和ACD，将实验观察结果与临床疾病以及基本机制与实际毒理学联系起来。
