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.
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-gamma 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 3H-thymidine uptake, and culture supernatants taken after 5 days were analysed for IL-5, IL-10 and IFN-gamma 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-gamma 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.


CONCLUSIONS
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.
Sachs
B
B
Department of Dermatology and Allergology, Rheinisch-Westfälische Technische Hochschule Aachen, Germany. Bernhardt.Sachs@post.rwth-aachen.de
Erdmann
S
S
Malte Baron
J
J
Neis
M
M
al Masaoudi
T
T
Merk
H F
HF
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002648:Child; D004342:Drug Hypersensitivity / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013995:Time
D000939:Epitopes; D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma