Drug-specific in vitro release of IL-2, IL-5, IL-13 and IFN-gamma in patients with delayed-type drug hypersensitivity.
BACKGROUND
The most prevalent drug hypersensitivity reactions are T-cell mediated. The only established in vitro test for detecting T-cell sensitization to drugs is the lymphocyte transformation test, which is of limited practicability. To find an alternative in vitro method to detect drug-sensitized T cells, we screened the in vitro secretion of 17 cytokines/chemokines by peripheral blood mononuclear cells (PBMC) of patients with well-documented drug allergies, in order to identify the most promising cytokines/chemokines for detection of T-cell sensitization to drugs.


METHODS
Peripheral blood mononuclear cell of 10 patients, five allergic to beta-lactams and five to sulfanilamides, and of five healthy controls were incubated for 3 days with the drug antigen. Cytokine concentrations were measured in the supernatants using commercially available 17-plex bead-based immunoassay kits.


RESULTS
Among the 17 cytokines/chemokines analysed, interleukin-2 (IL-2), IL-5, IL-13 and interferon-gamma (IFN-gamma) secretion in response to the drugs were significantly increased in patients when compared with healthy controls. No difference in cytokine secretion patterns between sulfonamide- and beta-lactam-reactive PBMC could be observed. The secretion of other cytokines/chemokines showed a high variability among patients.


CONCLUSIONS
The measurement of IL-2, IL-5, IL-13 or IFN-gamma or a combination thereof might be a useful in vitro tool for detection of T-cell sensitization to drugs. Secretion of these cytokines seems independent of the type of drug antigen and the phenotype of the drug reaction. A study including a higher number of patients and controls will be needed to determine the exact sensitivity and specificity of this test.
Lochmatter
P
P
Clinic of Rheumatology and Clinical Immunology/Allergology, Inselspital, Bern University Hospital, University of Bern, Switzerland.
Beeler
A
A
Kawabata
T T
TT
Gerber
B O
BO
Pichler
W J
WJ
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004342:Drug Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000819:agonists / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012882:Skin Tests; D013424:Sulfanilamides / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D047090:beta-Lactams / Q000276:immunology / Q000494:pharmacology
D016207:Cytokines; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D013424:Sulfanilamides; D047090:beta-Lactams; D007371:Interferon-gamma