RESEARCH - Evidence for a pathogenetic role of IL-18 in cutaneous lupus

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Arthritis Rheum. 2008 Sep 29;58(10):3205-3215.

Evidence for a pathogenetic role of interleukin-18 in cutaneous lupus

erythematosus.

Wang D, Drenker M, Eiz-Vesper B, Werfel T, Wittmann M.

Hannover Medical School, Hannover, Germany.

OBJECTIVE: Cutaneous manifestations are the most common clinical

features of lupus erythematosus (LE). The aim of this study was to

analyze differences in the inflammatory response of keratinocytes from

patients with cutaneous LE (CLE) compared with healthy controls.

METHODS: Keratinocytes from LE patients and controls were cultured

from epidermal stem cells of the hair follicle of anagen head hairs.

Functional responses of keratinocytes to cytokine stimulation were

determined by flow cytometry and enzyme-linked immunosorbent assay.

Biopsy samples of lesional skin were analyzed by immunohistochemistry.

RESULTS: Keratinocytes from CLE patients expressed higher levels of

IL-18 receptor on their cell surface in response to tumor necrosis

factor alpha (TNFalpha) or interferon-gamma stimulation. In response

to IL-18 stimulation, these cells produced large amounts of TNFalpha.

Of note, in the presence of IL-18, CLE keratinocytes failed to express

IL-12. IL-12 has previously been shown to protect keratinocytes from

ultraviolet irradiation-induced apoptosis. Keratinocytes from LE

patients were more prone to die upon exposure to IL-18, and this

increased apoptosis was abrogated by blockade of endogenously produced

TNFalpha as well as by the addition of exogenous IL-12. IL-18 was

highly expressed in biopsy samples of lesional skin from CLE patients.

CONCLUSION: Our results demonstrate an intrinsic difference in the

inflammatory response of keratinocytes and indicate an autocrine

feedback loop involving TNFalpha, IL-18, and IL-12 family members. Our

results suggest that IL-18 may occupy an important position in the

cytokine hierarchy in CLE, indicating the potential benefit of a local

agent that blocks IL-18 activity in the treatment of the

manifestations of CLE.

PMID: 18821674

http://www.ncbi.nlm.nih.gov/pubmed/18821674

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