| Evetsm 2005-03-29, 7:14 pm |
| Speaking of IL-10.
Effects of systemic interleukin-10 therapy on psoriatic skin lesions:
histologic, immunohistologic, and molecular biology findings.
Asadullah K, Friedrich M, Hanneken S, Rohrbach C, Audring H,
Vergopoulos A, Ebeling M, Docke WD, Volk HD, Sterry W.
Institute of Medical Immunology and Department of Dermatology,
University Hospital Charite, Berlin Humboldt University, Berlin,
Germany. khusru.asadullah@schering.de
Interleukin-10 is an important anti-inflammatory and immunosuppressive
cytokine with major impact on several immune reactions, including
regulatory mechanisms in the skin. Recently, we performed a phase II
trial in psoriatic patients receiving subcutaneously interleukin-10
over 7 wk. The clinical response suggested that interleukin-10 might
represent a novel anti-psoriatic drug. In order to understand better
the mode of action and to elucidate the effects of systemic
interleukin-10 treatment on the skin immune system, skin punch biopsies
from sites different from interleukin-10 injection were analyzed.
Biopsies were obtained from the patients before, at the end, and 3 wk
after interleukin-10 therapy. The results are reported here. Histologic
examination showed a decrease of several parameters reflecting the
psoriatic disease activity as acanthosis and extension of the horny
layer. Immunohistologic examination demonstrated decreasing numbers of
infiltrating T cells, dermal CD1a+ cells, and a diminished
proliferation of epidermal cells. Using a novel, quantitative reverse
transcriptase-polymerase chain reaction approach a significant shift
within the cytokine pattern was found. Interleukin-10 therapy led to a
decrease of cutaneous interleukin-8 and interleukin-10 mRNA expression.
Whereas no significant changes of interleukin-6, tumor necrosis
factor-alpha, and interferon-gamma expression were found, interleukin-4
was strongly upregulated suggesting a shift from a type 1 towards a
type 2 cytokine pattern. The changes within the local cytokine pattern
seem to be disease-related, as an inverse course was found in a single
interleukin-10 nonresponding patient. Our findings demonstrate
considerable effects of systemic interleukin-10 application on the skin
immune systems, which might contribute to the anti-psoriatic activity
of interleukin-10.
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