Determination of interleukin‐5 secretion from drug‐specific activated ex vivo peripheral blood mononuclear cells as a test system for the in vitro detection of drug sensitization

Abstract

Summary: Background In vitro detection of drug sensitization is still limited. The lymphocyte transformation test, which determines drug‐specific proliferation, is the only in vitro test for detecting drug sensitization at the cellular level irrespective of the reaction's clinical phenotype. Accumulation of eosinophils following IL‐5 secretion from drug‐specific stimulated T cells is a characteristic histological feature of drug‐induced skin eruptions. Objective We determined whether in vitro drug‐specific activation of ex vivo peripheral blood mononuclear cells from 10 patients with drug‐induced maculopapular exanthems and three patients with severe skin reactions results in secretion of IL‐5, IL‐10 or IFN‐γ and assessed the sensitivity and specificity of drug‐specific IL‐5 secretion as a test system compared with the lymphocyte transformation test and patch tests. Furthermore, the subsets of CD4+ and CD8+ T cells involved in drug‐specific proliferation, IL‐5 secretion and mRNA expression were examined in three patients. Methods Drug‐specific proliferation of peripheral blood mononuclear cells in the lymphocyte transformation test was investigated by 3 H‐thymidine uptake, and culture supernatants taken after 5 days were analysed for IL‐5, IL‐10 and IFN‐γ concentrations by ELISA technique. IL‐5 mRNA expression was determined by RT‐PCR. Results Drug‐specific activation of peripheral blood mononuclear cells consistently resulted in IL‐5 and to a lesser extent in IL‐10 and IFN‐γ secretion. The sensitivities of the patch test, lymphocyte transformation test and assessment of drug‐specific IL‐5 secretion for the detection of drug sensitization were 55%, 75% and 92%, respectively. Conclusion These data suggest a role for the determination of drug‐specific IL‐5 secretion by ex vivo peripheral blood mononuclear cells for the in vitro detection of drug‐sensitization in drug‐induced maculopapular exanthems.