| Autor: |
Reich K; Department of Dermatology, Georg-August-University, Von-Siebold-Strasse 3, 37075 Göttingen, Germany. kreich@gwdg.ge, Garbe C, Blaschke V, Maurer C, Middel P, Westphal G, Lippert U, Neumann C |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of investigative dermatology [J Invest Dermatol] 2001 Feb; Vol. 116 (2), pp. 319-29. |
| DOI: |
10.1046/j.1523-1747.2001.01248.x |
| Abstrakt: |
Psoriasis is a chronic inflammatory skin disease in which epidermal hyperplasia results from the release of cytokines by infiltrating type 1 T cells. Up- regulation of endogenous interleukin-10 controls type 1 skin responses in animal models; however, interleukin-10 production is low in psoriatic lesions. Consistent with an important role of interleukin-10 in psoriasis, we and colleagues have recently demonstrated clinical efficacy of subcutaneous administration of recombinant interleukin-10 to affected patients. Here, we studied the effects of interleukin-10 on disease-related inflammatory pathways. Patients were treated with recombinant interleukin-10 over 6 wk in an open-label phase II clinical trial. Tissue was obtained before and after therapy and examined by histology/immunohistochemistry, in situ hybridization, and quantitative real-time reverse transcription-polymerase chain reaction. Ten of 14 patients showed a marked reduction of the clinical disease activity. The clinical response was associated with a significant decrease of cutaneous T cell infiltration and the lesional expression of type 1 cytokines interferon-gamma and tumor necrosis factor-alpha. Interleukin-10 inhibited the epidermal interleukin-8 pathway by downregulating the expression of interleukin-8, its receptor CXCR2, and its inducer interleukin-17, and partially reversed the aberrant keratinocyte maturation defining psoriatic epidermal pathology. Remarkably, there was evidence that genetic factors are involved in the response to interleukin-10 as individual variations in the downregulation of tumor necrosis factor-alpha were related to the presence of polymorphisms in the tumor necrosis factor-alpha promoter. These data suggest that excessive production of type 1 cytokines in human skin disease can be counter-regulated by the administration of recombinant interleukin-10. Genotypic analysis may help to identify patients that will preferentially respond to interleukin-10 therapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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