Expression of interleukin-18 and caspase-1 in cutaneous T-cell lymphoma.
OBJECTIVE
Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-homing Th2 T cells. Clonal T cells and CTCL skin lesions typically express Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-10, but fail to produce Th1 cytokines. However, the reason for Th2 bias is unknown. IL-18 is a pleiotropic proinflammatory cytokine produced by monocytes/macrophages lineage as well as epithelial cells, such as human keratinocytes. In the absence of IL-12, IL-18 leads to increased immunoglobulin E production from B cells and enhanced production of IL-4 and IL-13 by basophils, mast cells, and CD4(+) T cells. We have analyzed cytokines in CTCL patients, which may bias the immune response around the Th1/Th2 axis.


METHODS
We examined plasma of 95 CTCL patients and skin of 20 CTCL patients for IL-18, caspase-1, IL-12, and other cytokines. To identify the presence or absence of these cytokine proteins in CTCL and normal skin, we cultured explants from skin biopsies on three-dimensional matrices.


RESULTS
Plasma levels of IL-18 and its converting enzyme, caspase-1, were significantly elevated in CTCL. mRNA levels for these factors were also elevated in CTCL skin lesions. Matrices populated with CTCL lesional skin produced significant amounts of IL-18 and caspase-1; however, production of IL-12 protein was barely detectable.


CONCLUSIONS
We propose that the high levels of IL-18 expression in lesional CTCL skin contribute to increased plasma levels of IL-18 and that this, in the face of significantly lower levels of IL-12, may contribute to the Th2 bias seen in this disease.
Yamanaka
Kei-ichi
K
Harvard Skin Disease Research Center, Department of Dermatology, Brigham and Women's Hospital, Boston, MA, USA.
Clark
Rachael
R
Dowgiert
Rebecca
R
Hurwitz
Daniel
D
Shibata
Michio
M
Rich
Benjamin E
BE
Hirahara
Kazuki
K
Jones
David A
DA
Eapen
Sara
S
Mizutani
Hitoshi
H
Kupper
Thomas S
TS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D020170:Caspase 1 / Q000097:blood* / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics; D020382:Interleukin-18 / Q000097:blood* / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology
D020382:Interleukin-18; D012333:RNA, Messenger; D018664:Interleukin-12; D020170:Caspase 1