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

Abstract

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.

• Authors: B Sachs, S Erdmann, T Al-Masaoudi, H F Merk
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 144 Issue 2 Pg. 316-20 (Feb 2001) ISSN: 0007-0963 [Print] England
• PMID: 11251565 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Interleukin-5
• Immunoglobulin E
• Clorazepate Dipotassium

Topics

• Adult
• Clorazepate Dipotassium (adverse effects)
• Cytokines (biosynthesis)
• Drug Eruptions (diagnosis)
• Female
• Humans
• Immunoglobulin E (blood)
• In Vitro Techniques
• Interleukin-5 (metabolism)
• Lymphocyte Activation
• Microsomes, Liver (immunology)
• Skin Tests (methods)