ABSTRACT
The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated with calcipotriol (50 µg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed by flow cytometry. After 14 days of treatment with calcipotriol, a significant clinical and histological effect was seen; however, we found no differences in the frequency of CD4(+) and CD8(+) T cells or ILC between calcipotriol- and vehicle-treated skin. The main finding was a significant decrease in CD8(+) IL-17(+) T cells in skin-derived cells from calcipotriol-treated skin, which was further supported by the absence of CD8(+) IL-17(+) T cells in immunohistochemical staining of calcipotriol-treated skin. No changes in the frequency of IL-22(+) or IFN-γ(+) cells were observed. Our findings show that the vitamin D analogue calcipotriol reduces the frequency of CD8(+) IL-17(+) T cells in psoriasis lesions concomitant with clinical improvement.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Calcitriol/analogs & derivatives , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Adult , Aged , CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , Calcitriol/therapeutic use , Erythema/drug therapy , Erythema/immunology , Female , Humans , Interferon-gamma/metabolism , Interleukin-17/metabolism , Interleukins/metabolism , Lymphocyte Count , Male , Middle Aged , Psoriasis/immunology , Young Adult , Interleukin-22ABSTRACT
BACKGROUND: Psoriasis is associated with increased risk of cardiovascular disease (CVD), possibly due to chronic low-grade systemic inflammation. Systemic anti-inflammatory treatment might reduce the risk of CVD. OBJECTIVE: Our aim was to investigate if short-term treatment with methotrexate influences microvascular endothelial function (MEF), an early surrogate marker of atherosclerosis, in patients with psoriasis. METHODS: We prospectively studied a hospital cohort of patients with psoriasis. Measurements of MEF were performed with the Endo-PAT2000© device at baseline and after 8-10 weeks of treatment with methotrexate. At the same time points, we recorded anamnestic information, measured body mass index (BMI), waist and hip circumferences and blood pressure, and drew blood samples (lipid profile, HbA1 and hs-CRP). Psoriasis severity was evaluated by psoriasis area and severity index (PASI) and the dermatology life quality index (DLQI). RESULTS: A total of 32 patients with psoriasis were included. Median age was 46 (range 18-82) years, and 50% were men. Twenty-seven patients completed the study. After 8-10 weeks, median PASI had decreased significantly by 6.2 (from 9.8 to 3.6), and DLQI had decreased by 7 (from 9 to 2). No significant changes were observed in MEF, expressed by reactive hyperaemia index and augmentation index. Also, we saw no significant changes in BMI, waist-hip ratio, blood pressure and blood samples. CONCLUSION: Short-term treatment with methotrexate did not affect MEF in patients with psoriasis. Further studies are warranted.