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

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In this study, we demonstrated that the percentage of CLA+ T cells was significantly higher in peripheral blood of psoriatic patients than in normal control subjects. Previous studies have reported that CLA was expressed by 10% to 20% of peripheral blood T cells in normal healthy adults and the diffe­rences of the percentage of CLA+ T cells between psoriatic patients and normal control subjects were not significant. But we found that only 3.6% and 2.1% of peripheral blood T cells expressed CD3 / CLA and CD4 / CLA, respectively, in normal sub­jects but psoriatic patients had significantly greater percentages of CD3+CLA+ and CD4+CLA+ T cells (median 8.7% and 5.7%, respectively) than those of normal control subjects. Such differences between this study and previous studies may be due to the characteristics of the recruited patients such as age, sex, severity of psoriasis, duration of the disease, previous treatment for psoriasis, number of patients and racial difference. Our data suggests that a certain portion of skin-homing CLA+ T cells in peripheral blood may be psoriasis-specific T cells especially in patients with very severe psoriasis. In one report, acute stage of psoriasis less than 6 weeks, CLA+ T cells were correlated with disease severity.

We found that cyclosporine significantly reduced the percentage of CLA+ T cells in peripheral blood of psoriatic patients during the early phase of cyclosporine therapy (at 3 weeks after the initiation of the study). But after 3 weeks, the number of CD3+CLA+ and CD4+CLA+ T cells increased gra­dually and there was no difference in the percentage of CLA+ T cells between baseline (before treatment) and at 18 weeks (at the end of the study). This finding has not been reported previously. The exact cause of gradual recovery of the initially reduced CLA+ T cell number by cyclosporine treatment was unknown. One possible hypothesis is that there may be two subsets of CLA+ T cells. One subset is cyclosporine-sensitive and the other is cyclosporine- resistant. T cell proliferation involving CD28:B7 costimulatory signal pathway was associated with cyclosporine-resistant IL-2 gene expression. T cells infiltrated in upper levels of the dermis and epidermis may be of the cyclosporine-resistant subset and this would explain the ineffectiveness of topical cyclos­porine for psoriasis treatment. In the early phase of cyclosporine therapy, reduction of cyclosporine- sensitive CLA+ T cells results in a decrease of total CLA+ T cell percentage.
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The gradual increase of CLA+ T cell percentage after the early phase may be due to proliferation of cyclosporine-resistant CLA+ T cell subset. As cyclosporine treatment was continued, the expression of E-selectin on the endothelial cells were gradually and persistently diminished. E-selectin may be involved in one of the action mechanisms of cyclosporine on psoriasis and may be used as a marker for disease activity. In contrast to the gradual recovery of the CLA+ T cell numbers in peripheral blood to the level of baseline, reduction of diminished expression of E-selectin on the endothelial cells were maintained at the end of this study (18 weeks after the initiation of cyclos­porine therapy). These findings suggest that recruit­ment of skin-homing T cells to psoriatic skin lesions was inhibited by diminished expression of E-selectin on the endothelial cells. The average remission time for cyclosporine was only 6 weeks. E-selectin ex­pression may be an earlier event in recurrence of psoriasis since strong re-expression of E-selectin on the endothelial cells in the early-recurred psoriatic skin lesions was observed.

In summary, gradual increase of CLA+ T cell numbers to the level of baseline in peripheral blood at 18 weeks and re-expression of E-selectin on the endothelial cells in the recurred psoriatic skin lesion, may explain partly the short average relapse time of cyclosporine treatment for psoriasis. canadian pharmacy online