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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
- Source :
- Journal of Investigative Dermatology. (2):319-329
- Publisher :
- The Society for Investigative Dermatology, Inc.
-
Abstract
- 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.
- Subjects :
- Keratinocytes
Male
skin
T-Lymphocytes
medicine.medical_treatment
Down-Regulation
Dermatitis
Inflammation
Dermatology
Biology
Biochemistry
Receptors, Interleukin-8B
Th1
030207 dermatology & venereal diseases
03 medical and health sciences
Th2
0302 clinical medicine
Psoriasis
medicine
Humans
Interleukin 8
Promoter Regions, Genetic
Molecular Biology
030304 developmental biology
0303 health sciences
Polymorphism, Genetic
Tumor Necrosis Factor-alpha
Interleukin-8
Cell Differentiation
Cell Biology
Immunotherapy
medicine.disease
Interleukin-10
3. Good health
Interleukin 10
medicine.anatomical_structure
Cytokine
inflammation
Immunology
Cytokines
Female
Tumor necrosis factor alpha
immunotherapy
Epidermis
medicine.symptom
Keratinocyte
Cell Division
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 0022202X
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....0331c7362e89299e6eaaf78a1e4250ac
- Full Text :
- https://doi.org/10.1046/j.1523-1747.2001.01248.x