Cytokine and chemokine expression in the skin from patients with maculopapular exanthema to drugs.
BACKGROUND
Maculopapular exanthema (MPE) is the most frequent clinical manifestation of nonimmediate allergic reactions to drugs and T helper 1 (Th1) cytokines and CD4(+) T cells have been shown to play an important role in its pathogenesis. We assessed the role of cytokines and chemokines and their receptors in the pathogenesis of MPE.


METHODS
We evaluated skin biopsies and peripheral CD4(+) and CD8(+) T cells from 27 patients during the acute phase of the reaction and 26 exposed controls. Semiquantitative real-time PCR was performed to determine the expression of cytokines and chemokines and their receptors and immunohistochemistry was used to determine the same chemokines and their receptor proteins in skin.


RESULTS
There was a high expression of the Th1 cytokines interferon-gamma (P = 0.006) and tumor necrosis factor-alpha (P = 0.022) in skin and CD4(+) T cells (P = 0.007 and P = 0.005, respectively); and of the Th1 chemokines CXCL9 (P = 0.005) and CXCL10 (P = 0.028) in the skin, while their receptor CXCR3 was increased in skin (P = 0.006) and CD4(+) T cells (P = 0.03). Homing chemokine receptors were also increased: CCR6 in skin (P = 0.026) and CD4(+) T cells (P = 0.016), and CCR10 only in CD4(+) T cells (P = 0.016), as well as their ligands, CCL20 and CCL27, in skin alone. Immunohistochemistry confirmed these results.


CONCLUSIONS
These data show significant differences in the expression of chemokines and chemokine receptors, related with a Th1 profile, in both skin biopsies and peripheral CD4(+) T cells in patients with drug-induced MPE.
Fernandez
T D
TD
Research Laboratory for Allergic Diseases, Carlos Haya Hospital-Fundacion IMABIS, Málaga, Spain.
Mayorga
C
C
Torres
M J
MJ
Cornejo-Garcia
J A
JA
López
S
S
Chaves
P
P
Rondon
C
C
Blanca
M
M
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054418:Chemokine CCL20 / Q000276:immunology / Q000378:metabolism; D054425:Chemokine CCL27 / Q000276:immunology / Q000378:metabolism; D054357:Chemokine CXCL10 / Q000276:immunology / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000276:immunology / Q000378:metabolism; D003875:Drug Eruptions / Q000276:immunology* / Q000378:metabolism; D005076:Exanthema / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D054418:Chemokine CCL20; D054425:Chemokine CCL27; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma