Homey B, von Schilling C, Blümel J, Schuppe H C, Ruzicka T, Ahr H J, Lehmann P, Vohr H W
Department of Dermatology, University of Düsseldorf, Germany.
Toxicol Appl Pharmacol. 1998 Nov;153(1):83-94. doi: 10.1006/taap.1998.8535.
Contact and photocontact allergic as well as irritant and photoirritant skin reactions represent a major problem in clinical dermatology and during the development of new pharmaceuticals. Furthermore, there is a lack of in vitro and in vivo assays that provide a clear differentiation between allergic and irritant skin reactions. Here, we describe an integrated model to differentiate between chemical-induced allergic and irritant skin reactions by measuring objective and easy-to-determine parameters within both skin and skin-draining lymph nodes. Dose-response studies with standard contact and photocontact allergens as well as irritants and photoirritants revealed that irritants predominantly induced skin inflammation, which in turn stimulated draining lymph node cell proliferation. In contrast, the induction phase of contact or photocontact allergy was characterized by marginal skin inflammation, but a marked activation and proliferation of skin-draining lymph node cells. Therefore, a differentiation index (DI) was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern whereas DI < 1 demonstrates an irritant potential of a chemical. Experiments with the contact allergen oxazolone, the photocontact allergen TCSA + UVA, the irritant croton oil, and the photoirritant 8-methoxypsoralen + UVA confirmed the predictive value of DI. Furthermore, flow cytometric analysis of lymph node-derived T- and B-cell subpopulations revealed that contact sensitizer, but not irritant, induced the expression of CD69 on the surface of I-A+ cells. In conclusion, further studies with a broad range of irritants and allergens will be required to confirm general applicability.
接触性和光接触性过敏以及刺激性和光刺激性皮肤反应是临床皮肤科和新药物研发过程中的一个主要问题。此外，缺乏能够明确区分过敏性和刺激性皮肤反应的体外和体内试验。在此，我们描述了一种综合模型，通过测量皮肤和引流皮肤的淋巴结内客观且易于确定的参数，来区分化学诱导的过敏性和刺激性皮肤反应。对标准接触性和光接触性变应原以及刺激性和光刺激性物质进行的剂量反应研究表明，刺激性物质主要诱导皮肤炎症，进而刺激引流淋巴结细胞增殖。相比之下，接触性或光接触性过敏的诱导阶段其特征是皮肤炎症轻微，但引流皮肤的淋巴结细胞有明显激活和增殖。因此，定义了一个区分指数（DI），描述引流皮肤的淋巴结细胞激活（淋巴结细胞计数指数）与皮肤炎症（耳部肿胀）之间的关系。DI > 1表明是过敏反应模式，而DI < 1表明一种化学物质具有刺激性潜力。用接触性变应原恶唑酮、光接触性变应原TCSA + UVA、刺激性物质巴豆油和光刺激性物质8 - 甲氧基补骨脂素 + UVA进行的实验证实了DI的预测价值。此外，对淋巴结来源的T细胞和B细胞亚群进行的流式细胞术分析表明，接触性致敏剂而非刺激性物质诱导I - A+细胞表面CD69的表达。总之，需要用多种刺激性物质和变应原进行进一步研究以确认其普遍适用性。
