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Cyclosporin A suppresses ICAM-1 expression by papillary endothelium in healing psoriatic plaques
P Petzelbauer1, G Stingl, K Wolff
1Department of Dermatology I, University of Vienna Medical School, Austria.
Abstract:
To analyze the mode of action of Cyclosporin A (CsA) in psoriasis, we examined the phenotypic profile of resident and passenger skin cells in seven psoriatic patients before and after 2 weeks of CsA treatment using a large panel of monoclonal antibodies in a three-step immunoperoxidase technique. For comparison, skin biopsies from psoriatic patients receiving psoralen + UVA (PUVA) therapy were examined. Although both treatment protocols were equally effective in inducing resolution of psoriatic lesions, the phenotypic changes induced by CsA differed greatly from those seen after PUVA. In CsA-treated patients there was a dramatic reduction in the ICAM-1 expression by papillary endothelial cells, but density, pattern, and phenotype of infiltrating inflammatory cells remained essentially unchanged. In contrast, PUVA therapy had no visible effect on ICAM-1 expression by papillary endothelial cells, but resulted in a significant reduction of the hemopoietic resident and infiltrating mononuclear cells within the epidermis. These results favor, but do not prove, the assumption that the CsA regimen chosen in this study exerts its anti-psoriatic effect primarily at the level of the keratinocyte, i.e., by inhibiting events leading to keratinocyte proliferation as well as by interfering with the secretion of mediators responsible for ICAM-1 expression by papillary endothelial cells.
Insights
Cyclosporin A (CsA) effectively treats psoriasis by targeting keratinocytes, unlike PUVA therapy. CsA reduces ICAM-1 expression and keratinocyte proliferation, offering a distinct therapeutic mechanism for psoriasis.
Area of Science:
- Immunodermatology
- Pharmacology
Background:
- Psoriasis is a chronic inflammatory skin condition.
- Understanding the precise mechanism of action for immunosuppressants like Cyclosporin A (CsA) is crucial for optimizing treatment strategies.
Purpose of the Study:
- To elucidate the mode of action of Cyclosporin A (CsA) in psoriasis by analyzing phenotypic changes in skin cells.
- To compare the effects of CsA with psoralen + UVA (PUVA) therapy on psoriatic skin lesions.
Main Methods:
- Examined phenotypic profiles of skin cells in seven psoriatic patients before and after 2 weeks of CsA treatment.
- Utilized a large panel of monoclonal antibodies and a three-step immunoperoxidase technique.
- Compared findings with skin biopsies from psoriatic patients undergoing PUVA therapy.
Main Results:
- Both CsA and PUVA effectively resolved psoriatic lesions, but induced different phenotypic changes.
- CsA significantly reduced ICAM-1 expression by papillary endothelial cells, with minimal changes in inflammatory cell infiltration.
- PUVA did not affect ICAM-1 expression but reduced mononuclear cells in the epidermis.
Conclusions:
- CsA's anti-psoriatic effect likely involves direct action on keratinocytes, inhibiting proliferation and mediator secretion.
- CsA interferes with keratinocyte-related pathways and papillary endothelial cell ICAM-1 expression.
- The distinct mechanisms of CsA and PUVA highlight their different therapeutic targets in psoriasis treatment.
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