STUDIES OF THE EFFECT OF CYCLOSPORINE IN PSORIASIS INVIVO - COMBINED EFFECTS ON ACTIVATED LYMPHOCYTES-T AND EPIDERMAL REGENERATIVE MATURATION
STUDIES OF THE EFFECT OF CYCLOSPORINE IN PSORIASIS INVIVO - COMBINED EFFECTS ON ACTIVATED LYMPHOCYTES-T AND EPIDERMAL REGENERATIVE MATURATION
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DOI：
10.1111/1523-1747.ep12499782
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发表时间：
1992-03-01
影响因子：
6.5
通讯作者：
KRUEGER, JG
中科院分区：
文献类型：
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作者：
GOTTLIEB, AB;GROSSMAN, RM;KRUEGER, JG
环孢霉素（CSA）在体外可降低淋巴因子的合成和角质形成细胞的增殖，但其在体内治疗银屑病的作用机制尚不完全清楚。10例银屑病患者接受CSA（2-7.5 mg/kg/d）治疗，10例患者中有9例临床改善。使用免疫过氧化物酶和北方印迹分析，研究CSA治疗前和治疗后1-3个月的皮肤活检中免疫和角质形成细胞活化的证据。CSA治疗后，所有患者斑块中活化的IL-2受体+ T细胞数量平均减少60%。10例患者中有7例显示角质形成细胞HLA-DR表达减少; 7例中有5例显示γ-IP-10免疫反应性减少，表明CSA治疗后斑块中γ-干扰素水平下降。我们研究了CSA治疗对TGF-α，IL-6和角蛋白K16表达的影响，这三种标记物是角质形成细胞生长激活。角化细胞TGF-α和IL-6的表达在活动性银屑病表皮中升高，在CSA治疗后这些患者中没有改变。大多数患者（5/8）在CSA治疗后继续表达过度增殖角蛋白K16。我们的研究结果表明，环孢素在体内的主要直接作用机制是减少斑块中的T细胞活化，伴随着淋巴因子产生的减少。
Cyclosporine (CSA) decreases lymphokine synthesis and keratinocyte proliferation in vitro, but its in vivo mechanism of action in treating recalcitrant psoriasis is incompletely understood. Ten psoriasis patients were treated with CSA (2-7.5 mg/kg/d) with clinical improvement in nine of 10 patients. Skin biopsies before and after 1-3 months of CSA treatment were studied for evidence of immune and keratinocyte activation using immunoperoxidase and Northern blotting analysis. The number of activated, IL-2 receptor+ T cells in plaques after CSA treatment was reduced in all patients by a mean of 60%. Seven of 10 patients showed a decrease in keratinocyte HLA-DR expression; five of seven showed a decrease in gamma-IP-10 immunoreactivity, suggesting a decline in gamma interferon levels in plaques after CSA therapy.We studied the effect of CSA treatment in vivo on TGF-alpha, IL-6, and keratin K16 expression, three markers of keratinocyte growth activation. Expression of keratinocyte TGF-alpha and IL-6, which are elevated in active psoriatic epidermis, did not change in these patients after CSA treatment. The majority of patients (five of eight) continued to express the hyperproliferative keratin K16 after CSA treatment. Our results suggest that the predominant direct mechanism of action of Cyclosporine in vivo is a diminution of T-cell activation in plaques, with attendant decreased lymphokine production.