Subcutaneous administration of polymerized type I collagen downregulates interleukin (IL)-17A, IL-22 and transforming growth factor-ß1 expression, and increases Foxp3-expressing cells in localized scleroderma.
Clin Exp Dermatol
; 37(6): 599-609, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22731679
ABSTRACT
BACKGROUND:
Localized scleroderma (LS) is a disfiguring inflammatory autoimmune disease of the skin and underlying tissue. As in systemic sclerosis, a key feature is the presence of T cells in inflammatory lesions.AIM:
To evaluate the effect of polymerized type I collagen vs. methylprednisolone (MP) in LS, and to determine the influence of this polymerized collagen (PC) on CD4+ peripheral T cells expressing interleukin (IL)-4, IL-17A, interferon-γ and Forkhead box protein (Foxp)3, and on cells expressing transforming growth factor (TGF)-ß1, IL-17A, IL-22 and Foxp3 in the skin.METHODS:
In total, 16 patients with LS were treated for 3 months with monthly subcutaneous intralesional injections of 0.1 mL MP (giving a total dose of 20 mg/mL each month) and 15 patients were treated, with weekly subcutaneous intralesional injections of PC, ranging from 0.2 mL (equivalent to 1.66 mg collagen) for a lesion of 50 mm in size, up to a maximum of 1.0 mL (8.3 mg collagen) for a lesion > 100 mm in size, and followed up for a further 6 months. Skin biopsies were obtained from lesions at baseline (before treatment) and 9 months later (6 months after treatment end). Tissue sections were evaluated by histology and immunohistochemistry (IL-17A, IL-22, TGF-ß1 and Foxp3). CD4+ T-cell subsets were determined in peripheral blood by flow cytometry.RESULTS:
Abnormal tissue architecture was seen in the biopsies taken from patients treated with MP, whereas the PC treatment restored normal skin architecture. PC downregulated pro-inflammatory/profibrotic cytokine expression in peripheral cells, and upregulated the number of regulatory T cells (Tregs) in skin. PC was safe and well tolerated.CONCLUSIONS:
PC is not only an antifibrotic/fibrolytic agent but also an immunomodulator biodrug that restores the balance between T helper (Th)1, Th2, Th17 and Tregs, downregulates production of pro-inflammatory or profibrogenic cytokines (IL-17A, IL-22 and TGF-ß1), and renews skin architecture, without adverse effects.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Esclerodermia Localizada
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Interleucinas
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Interleucina-17
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Colágeno Tipo II
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Fatores de Transcrição Forkhead
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Fator de Crescimento Transformador beta1
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article