Evaluation of the Potential Role of Cytokines in Toxic Epidermal Necrolysis

Toxic epidermal necrolysis is a rare disease observed as a consequence of adverse reactions to drugs. It results in the widespread apoptosis of epidermal cells and has a high mortality rate. The mechanisms leading to this apoptosis are not yet elucidated. We investigated whether the cytokines presen...

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Veröffentlicht in:Journal of investigative dermatology 2004-11, Vol.123 (5), p.850-855
Hauptverfasser: Nassif, Amal, Moslehi, Homayoun, Le Gouvello, Sabine, Bagot, Martine, Lyonnet, Luc, Michel, Laurence, Boumsell, Laurence, Bensussan, Armand, Roujeau, Jean-Claude
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Sprache:eng
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Zusammenfassung:Toxic epidermal necrolysis is a rare disease observed as a consequence of adverse reactions to drugs. It results in the widespread apoptosis of epidermal cells and has a high mortality rate. The mechanisms leading to this apoptosis are not yet elucidated. We investigated whether the cytokines present in the blister fluid, which accumulates under necrotic epidermis, originated from T lymphocytes and may play a role in the propagation of keratinocyte apoptosis. Interferon gamma (IFN-γ), soluble tumor necrosis factor alpha (TNF-α), soluble Fas ligand (sFas-L) were present in much higher concentration in the blister fluids of 13 toxic epidermal necrolysis (TEN) patients than in control fluids from burns. The results of RT-PCR studies, however, indicated that only IFN-γ and to a lesser extent interleukin (IL)-18 were produced by mononuclear cells present in the fluid. That suggests that the other cytokines also present (TNF-α, sFas-L, IL-10) rather originated from activated keratinocytes. Fas-L was indeed overexpressed on the membranes of keratinocytes in lesional skin in situ. The Th1 profile of T lymphocyte activation found in the blister fluid of patients with TEN is consistent with a key role for drug-specific cytotoxic T lymphocytes (CTL) as previously reported, the activation of keratinocytes by IFN-γ making them sensitive to cell-mediated cytolysis. We propose the hypothesis that the production of Fas-L, TNF-α, and IL-10 by keratinocytes could be a defense mechanism against CTL rather than a way of propagating apoptosis among epidermal cells.
ISSN:0022-202X
1523-1747
DOI:10.1111/j.0022-202X.2004.23439.x