Effect of Cyclosporine on Peripheral Blood and Lesional Skin in Psoriatic Patients:

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The number of CLA+ T cells is significantly higher in peripheral blood of psoriatic patients than in normal control subjects

We first compared the number of CD3+CLA+, CD4+CLA+, and CD8+CLA+ T cells in peripheral blood of psoriatic patients with those of normal control subjects using FACS analysis. The per­centages of CD3+CLA+, CD4+CLA+, and CD8~CLA+ T cells were significantly higher in psoriatic patients than in normal control subjects £<0.01.

Fig. 1. Comparison of CD3+CLA+, CD4+CLA+, and CD8+CLA+ T cells in peripheral blood between psoriatic patients and normal control subjects using FACS analysis. The percentages of CD3+CLA+, CD4+ CLA+, and CD8+CLA+ T cells were significantly higher in psoriatic patients than normal control subjects (p < 0.01, p < 0.01, p < 0.05, respectively). Each dot represents one individual and central bars are the median values of eight subjects in each group.

Effect of cyclosporine on the number of CLA+ T cells in peripheral blood of psoriatic patients

To investigate the effect of cyclosporine on CLA+ T cells, we performed FACS analysis on peripheral blood of psoriatic patients taken at 0 (baseline, before treatment), 3, 6, 12, and 18 weeks after the initiation of cyclosporine treatment. In the early phase of cyclosporine therapy at 3 weeks after the initiation of treatment, the percentages of CD3+ CLA+ and CD4+CLA+ T cells were significantly reduced in comparison with those of the baseline (£><0.01, Fig. 2A and B). The suppressive effect of cyclosporine on CLA+ T cells in peripheral blood of psoriatic patients was gradually diminished after 3 weeks and the percentages of CD3+CLA+ and CD4+CLA+ T cells were restored to the level of baseline (before treatment) at 18 weeks after the initiation of cyclosporine treatment in all patients. The percentage of CD8+CLA+ T cells showed change similar to those of CD3+CLA+ and CD4+ CLA+ T cells but after 6 weeks of cyclosporine treatment. There was no significant difference between the percentage measured and the baseline (Fig. 2C). Fig. 3 is a representative two-dimensional flow cytometric profile of CD4+CLA+ T cells from peripheral blood of one psoriatic patient of this study.
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Fig. 2. Changes of CD3+CLA+ (Fig. 2A), CD4+CLA+ (Fig. 2B) and CD8+CLA+ (Fig. 2C) T cells in peripheral blood of psoriatic patients by cyclosporine treatment. Dosage of cyclosporine was 3 mg/kg per day. At 3 weeks after the initiation of cyclosporine therapy, the percentages of CD3+CLA+, CD4+CLA+ and CD8+CLA+T cells examined by FACS were signi­ficantly reduced in comparison with those of the baseline (p < 0.01). But at the end of the study (at 18 weeks), the percentages of CD3+CLA+, CD4+ CLA+ and CD8+CLA+T cells were restored to the level of the baseline and there was no significant difference between baseline and at 18 weeks. Data are the mean ± SD of eight psoriatic patients.

Cyclosporine reduces expression of E-selectin on endothelial cells in psoriatic skin lesions

Normal skin samples showed no detectable E- selectin expression in our study. Blind scoring of the samples by 3 dermatologists showed strong (3+) intensity of E-selectin in upper dermal endothelial cells before cyclosporine treatment (Fig. ЗА). Mo­derate (2+) to strong (3+) expression of E-selectin in upper dermal endothelial cells was observed after 3 weeks of cyclosporine treatment (Fig 3B). After 6 and 12 weeks of cyclosporine treatment, E-selectin positivity was not observed on endothelial cells (Fig. 3C and 3D). Among the 5 patients, 2 showed rapid recurrences within 1 month and skin samples were taken again. Anti E-selectin staining showed strong (3+) positivity in upper dermal endothelial cells (Fig. 3E) although perivascular lymphocytic infil­trates were much less than in the skin samples taken before cyclosporine treatment. buy kamagra tablets

Fig. 3. (A) Strong expression of E-selectin in upper dermal endothelial cells before cyclosporine treatment. (B) Moderate expression of E-selectin in upper dermal endothelial cells was observed after 3 weeks of cyclosporine treatment. (C, D) No expression of E-selectin after 6 weeks (C) and 18 weeks (D) of cyclosporine treatment. (E) Strong expression of E-selectin in the skin lesion at 4 weeks after recurrence (Immunoperoxidase with haematoxylin counters tain x 100).