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In vitro drug allergy detection system incorporating human liver microsomes in chlorazepate-induced skin rash: drug-specific proliferation associated with interleukin-5 secretion.

Author(s): Sachs B, Erdmann S, Al-Masaoudi T, Merk HF

Affiliation(s): Department of Dermatology and Allergology, University Hospitals, Rheinisch-Westfalische Technische Hochschule Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Bernhardt.Sachs@post.rwth-aachen.de

Publication date & source: 2001-02, Br J Dermatol., 144(2):316-20.

Publication type: Case Reports

BACKGROUND: Chlorazepate is a benzodiazepine often used for pre-operative anxiolysis. The central metabolite responsible for the pharmacological and probably for the adverse effects of most benzodiazepines, including chlorazepate, is N-desmethyldiazepam. We report a woman who developed a generalized exanthem 1 day after receiving chlorazepate and four other drugs related to anaesthesia for surgery of the larynx. Patch tests pointed to chlorazepate as the culprit drug for the skin rash. OBJECTIVES: The purpose of this study was to detect drug allergy to chlorazepate or a metabolite in vitro by means of the lymphocyte transformation test (LTT), and to determine the concentrations of the T-helper (Th) 2-type cytokine interleukin (IL)-5 and the Th1-type cytokine interferon (IFN) -gamma in the culture supernatants. METHODS: We performed an LTT with peripheral blood mononuclear cells from the patient and a control, employing human liver microsomes containing cytochrome P450 enzymes as a metabolizing system, in parallel cultures. IL-5 and IFN-gamma concentrations in the culture supernatants were assessed by enzyme-linked immunosorbent assay. RESULTS: In the LTT, no T-cell reactivity was observed to the parent compound chlorazepate, whereas coincubation of the drug with human liver microsomes yielded proliferative T-cell reactivity, which was associated with secretion of IL-5 but not of IFN-gamma. CONCLUSIONS: We conclude that addition of a metabolizing system may be advantageous for in vitro detection of T-cell reactivity to drug metabolites in the LTT.

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