Subjects with allergic reactions to drugs show in vivo polarized patterns of cytokine expression depending on the chronology of the clinical reaction.
BACKGROUND
The mechanisms involved in adverse drug reactions with an immunologic basis (ADRIB) can be antibody dependent, mainly IgE or T cell dependent (sensitized T cells). These mechanisms are regulated by a number of cytokines, including IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha, which follow the classical T(H)1/T(H)2 immunologic paradigm. Although evidence for this has been seen in ex vivo studies, the results are heterogeneous, and few in vivo studies have been carried out in subjects with ADRIB.


OBJECTIVE
We studied a group of patients who experienced either immediate reactions (n = 10) or nonimmediate reactions (n = 9) to drugs to determine the cytokine pattern profile during the acute stage of the response, as well as after recovery.


METHODS
PBMCs were taken at different time intervals of 24 hours or less and 7, 15, and 30 days after the onset of the reaction, and the specific cytokine transcription and production were determined by using quantitative competitive RT-PCR and ELISA, respectively.


RESULTS
There was a transient polarized pattern corresponding to a T(H)1 response with IL-2, IFN-gamma, and TNF-alpha in nonimmediate reactions and to a T(H)2 response with IL-4 in immediate reactions.


CONCLUSIONS
This is the first in vivo demonstration of these T(H)1/T(H)2 patterns in subjects with ADRIB and confirms that an immunologic process is occurring related to the mechanisms involved in the pathologic manifestation. These findings are relevant to the understanding of the pathophysiologic mechanisms involved in ADRIB, suggesting that further studies in this direction are warranted.
Posadas
S J
SJ
Research Unit for Allergic Diseases, Carlos Haya Hospital, Malaga, Spain.
Leyva
L
L
Torres
M J
MJ
Rodriguez
J L
JL
Bravo
I
I
Rosal
M
M
Fernandez
J
J
Juarez
C
C
Blanca
M
M
D000328:Adult; D016207:Cytokines / Q000097:blood* / Q000235:genetics; D004342:Drug Hypersensitivity / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4