Currently available test models for the differentiation of photoallergic and photoirritant reactions are extremely time consuming and the protocols are very heterogeneous. In vitro tests are of proven value in predicting irritant or toxic effects, but these tests fail to predict chemical-induced allergic side effects. We developed test systems for this endpoint which is not easily detected by existing assays. In a previous publication we were able to discriminate between a contact sensitizer and a skin irritant with a combination of primary ear swelling analysis and cell counting of the ear-draining lymph nodes [Toxicol. Appl. Pharm. 153 (1998) 83; Arch. Toxicol. 73 (2000) 501]. This combination of tests was called the Integrated Model for the Differentiation of chemical-induced allergic and irritant Skin reactions (IMDS). In addition, it had been shown before that inclusion of UV irradiation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Photoimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolones are known to induce photoreactions after oral but not dermal treatment, the aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treatment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were tested in this system. We found a good correlation between the results of UV light-irradiated IMDS and a guinea pig model with the quinolones as far as photoirritancy was concerned. This holds true also for the photoallergic standard olaquindox and the photoirritant standard 8-methoxypsoralen. However, in contrast to the guinea pig assays the IMDS is fast and extremely predictive for the risk of both photosensitization and photoirritancy depending on the route of exposure. Thus, the UV light-irradiated IMDS turned out to be a good tool for the preclinical risk assessment procedure in terms of discriminating photoreactions. In addition, flow cytometric analyses were used to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions.

译文

目前可用的用于区分光过敏和光刺激反应的测试模型非常耗时,并且协议非常不同。体外测试在预测刺激性或毒性作用方面具有已证明的价值,但是这些测试无法预测化学引起的过敏副作用。我们为此终点开发了测试系统,而现有的检测方法不容易检测到。在以前的出版物中,我们能够通过初级耳肿胀分析和耳引流淋巴结细胞计数的组合来区分接触敏化剂和皮肤刺激物 [毒理学。应用。Pharm。153 (1998) 83; Arch。毒理学。73 (2000) 501]。这种测试的组合被称为用于区分化学引起的过敏性和刺激性皮肤反应 (imd) 的综合模型。此外,之前已经表明,在局部淋巴结测定中包含紫外线照射能够区分皮肤应用后的光过敏与光刺激反应 [Photodermatol. Photoimmunol.Photomode.10 (1994) 57]。由于已知氟喹诺酮类药物在口服而不是皮肤治疗后会诱导光反应,因此本研究的目的是应用IMDS来快速可靠地区分口服治疗后由于氟喹诺酮类药物引起的光反应。在该系统中测试依诺沙星、洛美沙星、氧氟沙星、司帕沙星和BAY y 3118。就光刺激性而言,我们发现紫外线照射的IMDS结果与喹诺酮类豚鼠模型之间存在良好的相关性。光过敏标准喹乙醇和光刺激剂标准8-甲氧基补骨脂素也适用。然而,与豚鼠测定相反,IMDS是快速且非常可预测光敏性和光刺激的风险,具体取决于暴露途径。因此,就区分光反应而言,紫外线照射的imd被证明是临床前风险评估程序的好工具。此外,流式细胞仪分析用于强调以下事实: 在诱导光刺激反应后发生了与抗原无关的激活。

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