Analyses of cutaneous fluoroquinolones photoreactivity using the integrated model for the differentiation of skin reactions

Currently available test models for the differentiation of photoallergic an d photoirritant reactions are extremely time consuming and the protocols ar e very heterogeneous. In vitro tests are of proven value in predicting irri tant or toxic effects, but these tests fail to predict chemical-induced all ergic side effects. We developed test systems for this endpoint which is no t easily detected by existing assays. In a previous publication we were abl e to discriminate between a contact sensitizer and a skin irritant with a c ombination of primary ear swelling analysis and cell counting of the ear-dr aining 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 reaction s (IMDS). In addition, it had been shown before that inclusion of UV irradi ation in the local lymph node assay enables discrimination of photoallergic from photoirritant reactions after dermal application [Photodermatol. Phot oimmunol. Photomed. 10 (1994) 57]. Because of the fact that fluoroquinolone s are known to induce photoreactions after oral but not dermal treatment, t he aim of the present study was to apply the IMDS for the fast and reliable differentiation of photoreactions due to fluoroquinolones after oral treat ment. Enoxacin, lomefloxacin, ofloxacin, sparfloxacin and BAY y 3118 were t ested 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 Ear as photoirritancy was concerned. This holds true also for the photoallergic s tandard olaquindox and the photoirritant standard 8-methoxypsoralen. Howeve r, in contrast to the guinea pig assays the IMDS is fast and extremely pred ictive 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 d iscriminating photoreactions. In addition, flow cytometric analyses were us ed to underline the fact that antigen-independent activation occurred after the induction of photoirritant reactions. (C) 2000 Elsevier Science B.V. A ll rights reserved.