indication-specific file folder for psoriasis and/or chronic inflammation
first file entry..........
J Invest Dermatol 2001 Feb;116(2):319-329
Response of Psoriasis to Interleukin-10 is Associated with Suppression of
Cutaneous Type 1 Inflammation, Downregulation of the Epidermal
Interleukin-8/CXCR2 Pathway and Normalization of Keratinocyte
Maturation.
Reich K, Garbe C, Blaschke V, Maurer C, Middel P, Westphal G, Lippert U, Neumann
C
Department of Dermatology, Georg-August-University, Gottingen, Germany; Department of
Dermatology, Eberhard-Karls-University, Tubingen, Germany; Department of Pathology,
Georg-August-University, Gottingen, Germany; Department of Occupational Medicine,
Georg-August-University, Gottingen, Germany.
[Record supplied by publisher]
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. |
