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- Title
Cyclosporin A Rapidly Inhibits Epidermal Cytokine Expression in Psoriasis Lesions, But Not in Cytokine-Simulated Cultured Keratinocytes.
- Authors
Elder, James T.; Hammerberg, Craig; Cooper, Kevin D.; Kojima, Takayuki; Nair, Rajan P.; Ellis, Charles N.; Voorhees, John J.
- Abstract
To better understand the cellular target(s) of cyclosporin action in psoriasis, we have studied the effects of systemic short-term (7 d), low-dose (3-7.5 mg/kg) cyclosporin A administration on the expression of the cytokines interleukin (IL)-8 and IL-1 β in psoriatic lesions. RNA blot hybridization analysis of pretreatment keratome biopsies revealed that expression of both cytokine mRNAs was highly variable from patient to patient. Significant covariation of both cytokine mRNA levels was noted (r = 0.86, p < 0.0001). However, there was no significant correlation between expression of either cytokine and clinical severity, as measured by the retreatment Psoriasis Area and Severity Index (PASI). IL-1 β protein levels measured by enzyme-linked immunosorbent assay (ELISA) were highly correlated with IL-1 β mRNA levels, indicating that the differences in transcript levels accurately reflect differences in epidermal cytokine protein. Significant reductions in both cytokine transcripts and in IL-1 β immunoreactive protein were noted in the high expression subgroup after 1 week of cyclosporin A therapy, prior to detectable clinical improvement. In contrast to its pronounced effects on epidermal cytokine expression <em>in vivo</em> and the allogeneic mixed lymphocyte reaction <em>in vitro</em>, cyclosporine A did not inhibit the induction of intercellular adhesion molecule (ICAM)-1 or IL-8 mRNAs by cultured keratinocytes in response to IL-1 β or the combination of tumor necrosis factor (TNF)-α and interferon (IFN)-β. These data suggest that epidermal keratinocytes respond to signals produced by activated T cells by coordinate expression of multiple cytokines, and that cyclosporin A acts primarily through blockade of T cells, rather than through keratinocyte activation.
- Subjects
SKIN diseases; PSORIASIS; CYCLOSPORINE; KERATINOCYTES; PHARMACOKINETICS; RNA; NUCLEIC acid hybridization; BIOPSY; CELL culture
- Publication
Journal of Investigative Dermatology, 1993, Vol 101, Issue 6, p761
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12371691