Comparison of the effects of vitamin D products in a psoriasis plaque test and a murine psoriasis xenograft model

被引:18
作者
Kvist, Peter H. [2 ]
Svensson, Lars [2 ]
Hagberg, Oskar [3 ]
Hoffmann, Vibeke [4 ]
Kemp, Kaare [2 ]
Ropke, Mads A. [1 ]
机构
[1] LEO Pharma AS, Translat Res, DK-2750 Ballerup, Denmark
[2] LEO Pharma AS, Dept Dis Pharmacol, DK-2750 Ballerup, Denmark
[3] LEO Pharma AS, Dept Biostat, DK-2750 Ballerup, Denmark
[4] LEO Pharma AS, Dept Clin Operat, DK-2750 Ballerup, Denmark
关键词
ONCE-DAILY TREATMENT; T-CELL SUBSETS; EPIDERMAL PROLIFERATION; BETAMETHASONE DIPROPIONATE; CALCIPOTRIOL OINTMENT; DOUBLE-BLIND; COMBINATION; VULGARIS; KERATINIZATION; POPULATIONS;
D O I
10.1186/1479-5876-7-107
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The aim of the present study was to compare the effects of Daivobet (R) and calcipotriol on clinical score and biomarker responses in a modified version of the Scholtz-Dumas psoriasis plaque assay. Furthermore, it was the aim to compare the effects of calcipotriol and betamethasone in the murine psoriasis xenograft model. Twenty four patients with psoriasis were treated topically once daily for three weeks, whereas the grafted mice were treated for four weeks. Clinical responses were scored twice weekly and biopsies were taken at the end of each study to analyse for skin biomarkers by histology and immunohistochemistry. The results clearly demonstrate effects on both clinical signs and biomarkers. In the patient study the total clinical score was reduced significantly with both Daivobet (R) and calcipotriol. Both treatments reduced epidermal thickness, Ki-67 and cytokeratin 16 expression. T cell infiltration was significantly reduced by Daivobet (R) but only marginally by calcipotriol. Both treatments showed strong effects on the epidermal psoriatic phenotype. Results from the xenograft model essentially showed the same results. However differences were observed when investigating subtypes of T cells. The study demonstrates the feasibility of obtaining robust biomarker data in the psoriasis plaque test that correlate well with those obtained in other clinical studies. Furthermore, the biomarker data from the plaque test correlate with biopsy data from the grafted mice.
引用
收藏
页数:9
相关论文
共 20 条
[1]   EPIDERMAL CYTOKERATIN AND IMMUNOCYTE RESPONSES DURING TREATMENT OF PSORIASIS WITH CALCIPOTRIOL AND BETAMETHASONE VALERATE [J].
BERTHJONES, J ;
FLETCHER, A ;
HUTCHINSON, PE .
BRITISH JOURNAL OF DERMATOLOGY, 1992, 126 (04) :356-361
[2]   Animal models of psoriasis [J].
Boehncke, Wolf-Henning ;
Schoen, Michael P. .
CLINICS IN DERMATOLOGY, 2007, 25 (06) :596-605
[3]  
DEJONG EMGJ, 1991, BRIT J DERMATOL, V124, P221
[4]  
DUMAS KJ, 1972, ACTA DERM-VENEREOL, V52, P43
[5]  
Glade CP, 1996, BRIT J DERMATOL, V135, P379
[6]   Psoriasis 1 - Pathogenesis and clinical features of psoriasis [J].
Griffiths, Christopher E. M. ;
Barker, Jonathan N. W. N. .
LANCET, 2007, 370 (9583) :263-271
[7]   Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial [J].
Guenther, L ;
Cambazard, F ;
Van de Kerkhof, PCM ;
Snellman, E ;
Kragballe, K ;
Chu, AC ;
Tegner, E ;
Garcia-Diez, A ;
Springborg, J .
BRITISH JOURNAL OF DERMATOLOGY, 2002, 147 (02) :316-323
[8]  
Jensen AM, 1998, BRIT J DERMATOL, V139, P984
[9]   A new calcipotriol/betamethasone dipropionate formulation (Daivobet™) is an effective once-daily treatment for psoriasis vulgaris [J].
Kaufmann, R ;
Bibby, AJ ;
Bissonnette, R ;
Cambazard, F ;
Chu, AC ;
Decroix, J ;
Douglas, WS ;
Lowson, D ;
Mascaro, JM ;
Murphy, GM ;
Stymne, B .
DERMATOLOGY, 2002, 205 (04) :389-393
[10]   A double-blind, randomized quantitative comparison of calcitriol ointment and calcipotriol ointment on epidermal cell populations, proliferation and differentiation [J].
Korver, J. E. M. ;
Vissers, W. H. P. M. ;
Van Rens, D. W. A. ;
Pasch, M. C. ;
Van Erp, P. E. J. ;
Boezeman, J. B. M. ;
Van De Kerkhof, P. C. M. .
BRITISH JOURNAL OF DERMATOLOGY, 2007, 156 (01) :130-137