Serum adenosine deaminase levels in patients with psoriasis: a prospective case-control study

Adenosine deaminase (ADA) activity is a nonspecific marker of T cell activation. T cell activation is thought to play an important role in the pathogenesis of psoriasis. Our purpose was to assess the significance of serum ADA activity in psoriasis and its relevance to disease activity. ADA activity was determined with an enzymatic method in 25 patients with psoriasis and in 15 healthy subjects. These measurements were repeated for 10 patients after either PUVA or cyclosporin A treatments. Disease activity was estimated by the PASI scoring system. Serum ADA level was significantly elevated in patients with psoriasis compared to healthy subjects (p<0.05). There was a significant decrease in the ADA levels after treatment compared to pretreatment values in the same patients (p<0.05). There was no correlation between ADA levels and PASI scores.These results support the evidence that T cell activation is involved in the pathogenesis of psoriasis and that ADA may be valuable in the assessment of disease activity in psoriasis.     

银屑病患者自身免疫性甲状腺炎调查分析

目的:调查我院银屑病患者中自身免疫性甲状腺炎的发生率。方法:纳入157例银屑病患者和年龄、性别及BMI相匹配的100例对照病例(非炎症性皮肤病患者)进行回顾性分析,测定三碘甲状腺原氨酸(T3)、甲状腺素(T4)、促甲状腺激素(TSH)、甲状腺球蛋白(TG)、甲状腺球蛋白抗体(TGAb)、抗甲状腺过氧化物酶抗体(TPOAb)水平。其中,TGAb和(或)TPOAb阳性界定为自身免疫性甲状腺炎。比较两组中自身免疫性甲状腺炎的发生率、甲状腺激素水平,并进行危险因素分析。结果:银屑病组中自身免疫性甲状腺炎发生率高于对照组(11.5%vs 9%),但两组间无明显差异(x~2=0.40,P>0.05)。银屑病中自身免疫性甲状腺炎的发生与发病年龄、病程、PASI评分和肥胖无关(P值均>0.05)。银屑病中血清TT3、FT3和TSH水平显著高于对照组(P<0.05),差异有统计学意义。结论:银屑病患者与正常人群相比,发生自身免疫性甲状腺炎的风险无增加;但血清T3可能在银屑病发病中发挥作用。     

红细胞趋化因子受体在寻常性银屑病患者外周血中性粒细胞中的表达

目的研究红细胞趋化因子受体(ECKR)在寻常型银屑病患者外周血中性粒细胞中的表达情况,探讨其在银屑病发病机制中的作用。方法应用流式细胞仪和特异性FITC标记的鼠抗人ECKR抗体检测寻常型银屑病患者和正常人外周血中性粒细胞表面ECKR蛋白的表达水平。应用逆转录-聚合酶链反应(RT-PCR)方法检测28例寻常型银屑病患者以及30例正常人外周血中中性粒细胞内ECKRmRNA的表达。并将结果与患者皮损面积及严重程度指数(PA-SI)进行了相关性分析。结果寻常型银屑病患者外周血中性粒细胞膜ECKR阳性率明显低于正常人,进行期患者较稳定期患者显著降低,且患者中性粒细胞膜ECKR的阳性率与其PASI评分呈负相关。患者外周血中性粒细胞内ECKRmR-NA的表达水平明显高于正常人,而进行期患者ECKRmRNA的表达又高于稳定期患者。结论ECKR在银屑病发病过程中发挥一定的作用,其表达水平与疾病的进展密切相关。     

Insulin‐like growth factor‐1 in psoriatic plaques treated with PUVA and methotrexate

Background The pathogenesis of psoriasis is thought to depend on the activation of immune cells and their secreted cytokines, chemokines and growth factors like IGF‐1 which may contribute to the epidermal hyperplasia of psoriasis. Treatment of psoriasis with PUVA and methotrexate are associated with clinical improvement and decrease in epidermal hyperplasia. Objective To examine the effects of PUVA and methotrexate therapy on IGF‐1 expression in psoriatic plaques and whether this change correlates with clinical response. Methods For 24 psoriatic patients, the PASI score and levels of lesional IGF‐1 and its mRNA were determined by RT‐PCR before and after treatment with either methotrexate or PUVA. Skin biopsies from 12 healthy volunteers served as control for IGF‐1 levels in normal skin. Results Lesional skin of psoriatic patients showed a statistically significant elevation in IGF‐1 and its mRNA levels in comparison to control (P = 0.0001). Both methotrexate and PUVA treatment were associated with a significant decrease in both PASI scores and lesional IGF‐1 after 10 month treatment. Conclusion Both methotrexate and PUVA therapy for psoriasis are associated with a decrease in PASI score and IGF‐1. The IGF‐1 down‐regulation may possibly be a consequence of the decrease in cytokines and inflammatory cellular infiltrate that occur following treatment with either modalities or due to their effect on local fibroblast activity and proliferation.     

Efficacy and Safety of Etanercept in Psoriasis after Switching from Other Treatments

Background: Since targeted biologic treatments have been introduced for the treatment of plaque-type psoriasis and psoriatic arthritis, switching between different medications has become necessary in selected patients, particularly after treatment failures. Objective: To evaluate the efficacy and safety of etanercept treatment in adult patients with psoriasis after failure to respond to other previous therapies. In particular, the differences in efficacy profiles after switching from traditional (cyclosporine [ciclosporin], methotrexate, retinoids, fumaric acid esters, psoralen plus UVA therapy, corticosteroids) or biologic (infliximab, efalizumab) treatments were analyzed. Methods: The study included 124 patients affected by plaque-type psoriasis who received etanercept administered subcutaneously at a dosage of 50 mg twice weekly for 12 weeks, followed by 25 mg twice weekly for an additional 12 weeks, and 110 patients affected by psoriatic arthritis who were treated with etanercept 25 mg twice weekly in a continuous regimen, after a 12-week period of treatment with etanercept 50 mg twice weekly. Results: Efficacy results were consistent in both groups of patients (plaque-type psoriasis and psoriatic arthritis), as expressed by the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 50 and PASI 75 scores. Among psoriatic arthritis patients, the mean pain Visual Analog Scale (VAS) score showed a substantial reduction during the treatment course, from 67.2 at week 0 to 15.8 at week 24. After 24 weeks, among patients with plaque-type psoriasis who had not previously received biologic therapies, 89.9% of patients achieved PASI 50 and 75.3% achieved PASI 75, while among patients who had received biologic therapies, 69.6% of patients achieved PASI 50 and 65.2% achieved PASI 75. In addition, 92.3% of patients with psoriatic arthritis who had not previously received biologic therapies achieved PASI 50 and 73.8% achieved PASI 75, while among patients who had received biologic therapies, 45.8% of patients achieved PASI 50 and 29.2% achieved PASI 75. Conclusions: Our study demonstrated that etanercept was more effective in those patients who had not previously received other biologic therapies than in those who had. The results of the present study indicate that etanercept may represent a valid, effective, and well tolerated therapeutic alternative even after failure to respond to traditional and other biologic therapies.     

CD26/dipeptidyl-peptidase IV and adenosine deaminase serum levels in psoriatic patients treated with cyclosporine, etanercept, and psoralen plus ultraviolet A phototherapy

Objective The aim of this study is to determine serum levels of soluble forms of CD26/dipeptidyl‐peptidase IV (DPP‐IV) and adenosine deaminase (ADA), thought to be markers of T‐cell activation, and changes in their levels in response to cyclosporine, etanercept, and psoralen plus ultraviolet A (PUVA) treatments with respect to disease activity. Methods This study is designed as a prospective clinical study with a control group and three months of follow‐up. The study included 41 patients with psoriasis and 41 healthy controls that were older than 18 years of age. There were three different treatment groups: PUVA (n = 15), cyclosporine (n = 15), and etanercept (n = 11). To determine disease severity of patients with psoriasis, psoriasis area and severity index (PASI) scores were calculated. Results Only mean serum ADA levels were different between patients with psoriasis [mean ± standard deviation (SD) = 13.9 ± 3.3 U/ml] and control group (mean ± SD = 12 ± 3.5 U/ml). Mean serum ADA levels were significantly higher before treatment than after treatment (mean ± SD = 12.4 ± 3.4 U/ml). Contrarily, following three months of therapy, mean serum CD26 levels increased significantly from 777.7 ± 214.6 to 835.3 ± 203 ng/ml (P < 0.05) and mean serum DPP‐IV activity increased significantly from 12.1 ± 4 to 15.9 ± 4.2 nmol/min (P < 0.05). There was no correlation between ADA and CD 26/DPP‐IV with PASI values. Conclusions The results show that ADA might be a useful marker indicating disease activity and T‐cell activation. As significant changes were observed in serum CD26/DPP‐IV before and after treatment, we think CD26/DPP‐IV might play a role in psoriasis pathogenesis, which should be clarified by further studies.     

银屑病患者红细胞免疫功能的研究

目的：明确银屑病特别是该病病情波动与红细胞免疫功能变化的关系。方法：检测１２３例银屑病患者和３５例正常人Ｅ－Ｃ３ｂＲＲ、Ｅ－ＩＣＲ,对其中５８例患者４周后作随访检测。结果：（１）银屑病患者Ｅ－Ｃ３ｂＲＲ、Ｅ－ＩＣＲ均较正常人高;（２）病程５年以上级较５年以下组病人的Ｅ－Ｃ３ｂＲＲ高;（３）ＰＡＳＩ与Ｅ－Ｃ３ｂＲＲ呈正相关;（４）ＰＡＳＩ的治疗前后变化值与Ｅ－Ｃ３ｂＲＲ变化值呈正相关。结论：银屑病患者红细胞免疫功能存在亢进和紊乱。红细胞免疫粘附功能试验可作为判断银屑病病情和预后的客观指标之一。     

Increased urine neopterin levels in psoriasis

The production of neopterin closely reflects activation of T-lymphocyte-mediated immunity. Oxidized and reduced forms of urine neopterin were measured by reversed-phase ion-pair high-performance liquid chromatography in patients with moderate to severe chronic plaque psoriasis (n = 40), and in a heterogeneous group of patients (n = 14) with cutaneous T-cell malignancies (CTCM). Results were compared with healthy non-psoriatic control subjects (n = 30). Neopterin levels were repeated after a course of ultraviolet B therapy (UVB) plus topical tar or dithranol, or photochemotherapy (PUVA), in 12 psoriatic patients. Fully oxidized urine neopterin levels and neopterin/creatinine ratios were significantly elevated in the psoriatic group compared with controls (P < 0.002, P < 0.05) but not in the CTCM group. Both neopterin and its creatinine ratio were significantly reduced by treatment (P < 0.05, P < 0.01). Psoriasis area and severity index scores (PASI) correlated strongly with urine neopterin levels (P < 0.001). These findings indicate that urine neopterin concentrations may be a marker of psoriatic disease activity, and further support the importance of activated T lymphocytes in the pathogenesis of psoriasis.     

银屑病患者血清和皮损中血管内皮细胞粘附分子的对比研究

目的 探讨银屑病患者血清和皮损中4种血管内皮粘附分子表达与银屑病疾病活动性之间的关系。方法 采用ELISA法检测36例银屑病患者治疗前后和36例健康人的血清中可溶性粘附分子（sICAM-1、sICAM-3、sVCAM-1、sELAM）的浓度。同时用ABC免疫组化染色技术检测了36例银屑病患者皮损和临床治愈处皮肤粘附分子（ICAM－1、ICAM－3、VCAM－1、ELAM）的表达情况。结果 与正常人相比，银屑病患者皮损部位4种粘附分子的原位表达呈明显上调（P＜0.005），同时患者血清中4种可溶性粘附分子浓度也明显升高（P＜0.001）。经治疗后银屑病患者皮损部位4种粘附分子的原位表达明显下调（P＜0.05），同时血清中4种可溶性粘附分子浓度比前也下降（P＜0.05）；血清中4种可溶性粘附分子的浓度与银屑病疾病活动严重指数（PASI）均呈正相关，但治疗前后sVCAM-1的水平上升和下降的幅度最大，且与PASI的相关性最好。结论 血管内皮细胞粘附分子参与银屑病的发病机制；患者血清中可溶性粘附分子浓度的升高可能与皮损部位血管内皮细胞上相应的粘附分子高表达有关；血清VCAM－1的水平可以作为反映银屑病疾病活动的一个新的敏感指标。     

Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label study

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-α (TNF-α) antagonist that decreases excessive levels of TNF-α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups ( P  < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.     

Adenosine deaminase activity,trypsin inhibitory capacity and total antioxidant capacity in psoriasis

Background Psoriasis is a chronic inflammatory skin disease characterized by pathological skin lesions because of various exogenous and endogenous factors and associated with a number of biochemical and immunological disturbances. Objective The aim of the present study was to determine the level of adenosine deaminase activity, serum trypsin inhibitory capacity and total antioxidant capacity of plasma in psoriatic patients. Subjects and methods The study was performed in controls (n = 46) and in psoriatic patients (n = 40). The patients were scored with PASI (psoriasis area and severity index). The serum ADA activity was determined using Aguisti and Galanti method and serum trypsin inhibitory capacity (sTIC) were measured by enzymatic assay. Besides, serum total antioxidant capacity was measured using ferric reducing ability of plasma. Results The serum ADA activity of the psoriatic patients was found to be significantly higher (P < 0.001) than that of the healthy control. We also found that the trypsin inhibitory capacity was significantly higher in patients than in control group (P < 0.001). Total antioxidant capacity of plasma was significantly lower in psoriatic patients than in healthy controls (P = 0.025). There were no significant correlations among ADA, TAC and TIC. Conclusion Serum ADA activity and sTIC were increased in psoriatic patients. In parallel, serum total anti‐oxidant activity was decreased in these patients.     

Effect of psoriasis therapy on VEGF and its soluble receptors serum concentrations

Background Vascular endothelial growth factor (VEGF) is recognized a pivotal pro‐angiogenic factor responsible for new blood vessels formation in psoriatic lesion. Objectives The aim of the study was to analyse serum concentrations of VEGF and its soluble receptors (sVEGF) R1 and R2 in psoriatic patients before and after treatment. Methods Serum samples were collected before and after 14 days of standard topical therapy, from 44 patients with exacerbated chronic plaque‐type psoriasis and VEGF, sVEGF R1 and sVEGF R2 concentrations were measured using an enzyme immunoassay. Data were analysed with respect to baseline values of the psoriasis area severity index (PASI). Results Baseline mean serum levels of VEGF and sVEGF R1, but not sVEGF R2 were significantly higher in patients than in healthy controls. VEGF demonstrated significant correlation with PASI score. Treatment resulted in significant reduction of VEGF serum concentration, particularly in patients with severe course of the disease (PASI >20) and increase in sVEGF R1 concentration in patients with mild disease activity (PASI <10). Moreover, serum sVEGF R1 level after treatment termination was significantly higher in patients with mild than severe course of psoriasis. Conclusions We confirmed the association between psoriasis activity and serum VEGF concentrations, which can be recognized as an indicator of the disease severity. However, the increase of serum sVEGF R1 concentrations can predict amelioration of clinical signs.     

Estimation of tissue osteopontin levels before and after different traditional therapeutic modalities in psoriatic patients

Background Several lines of evidences support a major role for Th1 cells in psoriasis. Treatment of psoriasis with cyclosporine, methotrexate and psoralen plus ultraviolet A (PUVA) is associated with clinical improvement and decrease in epidermal hyperplasia. Osteopontin (OPN) exerts a T‐helper type 1 (Th1) cytokine function, regulating inflammatory cell accumulation and function. Objective To detect the effects of methotrexate, cyclosporine and PUVA on OPN expression in psoriatic plaques, and whether these changes correlate with clinical response. Methods For three groups of psoriatic patients (each including 12 patients), the Psoriasis Area Severity Index (PASI) and levels of lesional skin OPN were determined using enzyme‐linked immunosorbent assays before and after treatment with methotrexate, cyclosporine or PUVA. Skin biopsies from 20 healthy volunteers served as control for OPN levels in normal skin. Results Baseline lesional skin of psoriatic patients showed a statistically significant elevation of OPN levels in comparison to controls. Three months after therapy, the three therapeutic modalities were associated with a significant decrease in the mean levels of PASI and tissue OPN, with the PUVA group showing the highest level of reduction in OPN levels and cyclosporine group showing the highest level of reduction in PASI. Conclusion Our study points to the possible role played by OPN in the pathogenesis of psoriasis and in reflecting disease severity. These standard therapeutic modalities used in the current study were associated with a significant decrease in PASI and OPN levels. They constitute highly effective therapeutic modalities for psoriasis, which might exert their anti‐psoriatic activity partially through altering the expression of OPN.     

银屑病患者外周血单个核细胞端粒酶活性及与疾病严重程度的关系

目的探讨银屑病患者外周血单个核细胞(PBMC)端粒酶活性及与疾病严重程度和病程的关系。方法分离银屑病患者和正常人外周血单个核细胞,采用聚合酶链反应-酶联免疫吸附(PCR-ELISA)法检测寻常型银屑病患者和正常人外周血单个核细胞的端粒酶活性水平;用银屑病皮损严重程度指数(PASI)评价银屑病患者病情严重程度。结果银屑病组PBMC的端粒酶活性(0.9±0.18)较正常组(0.49±0.11)显著升高(t=8.096,P<0.01),进行期(0.97±0.19)高于消退期或静止期(0.90±0.17),端粒酶活性与疾病严重程度成正相关(r=0.889,P<0.001),而与病程无明显线性关系。结论银屑病患者外周血单个核细胞端粒酶活性水平升高,且与疾病严重程度成正相关,而与病程无关,可作为银屑病发病及病情判定的一个指标。     

Neuropeptides and their receptors in psoriatic skin in relation to pruritus

BACKGROUND: Pruritus in patients with psoriasis has been reported to be more common than previously thought. OBJECTIVES: To determine the actual prevalence of pruritus in psoriasis according to severity of psoriasis and to verify the hypothesis of involvement of neuropeptides and their receptors in psoriatic pruritus. METHODS: We analysed questionnaire replies from 152 patients with chronic plaque-type psoriasis and we assayed the expression of neuropeptides and their receptors in lesional skin biopsies obtained from psoriatic patients with pruritus compared with those from psoriatic patients without pruritus, nonlesional skin of patients with pruritic psoriasis and normal controls by confocal laser scanning microscopy. RESULTS: Of the 152 patients with psoriasis, 112 (73.7%) had pruritus, and these patients had a higher mean Psoriasis Area and Severity Index (PASI) score than psoriatic patients without pruritus. There was positive correlation between the PASI score and the intensity of pruritus. Keratinocytes in the psoriatic plaques of patients with pruritus showed consistently increased expression of substance P receptor (SPR), high-affinity nerve growth factor receptor (TrkA) and calcitonin gene-related peptide receptor (CGRPR). CONCLUSIONS: Pruritus is a common feature in psoriasis. Considering the well-known roles of neuropeptides in pathogenesis of both psoriasis and pruritus, increased SPR, TrkA and CGRPR may be involved in the pathogenesis of pruritus in psoriasis and in the severity of psoriasis.     

Effects of administration of a single dose of a humanized monoclonal antibody to CD11a on the immunobiology and clinical activity of psoriasis

BACKGROUND: CD11a/CD18 comprise subunits of leukocyte function associated antigen (LFA-1), a T-cell surface molecule important in T-cell activation, T-cell emigration into skin, and cytotoxic T-cell function. OBJECTIVE: We explored the immunobiologic and clinical effects of treating moderate to severe psoriasis vulgaris with a single dose of humanized monoclonal antibody against CD11a (hu1124). METHODS: This was an open label study with a single dose of hu1124 at doses of 0.03 to 10 mg/kg. Clinical (Psoriasis Area and Severity Index [PASI]) and immunohistologic parameters (epidermal thickness, epidermal and dermal T-cell numbers, and keratinocyte intercellular adhesion molecule 1 [ICAM-1] expression) were followed. RESULTS: Treatment with hu1124, at doses higher than 1.0 mg/kg (group III), completely blocks CD11a staining for at least 14 days in both blood and psoriatic plaques. At 0.3 to 1.0 mg/kg, T-cell CD11a staining was completely blocked; however, blockade lasted less than 2 weeks (group II). Only partial saturation of either blood or plaque cellular CD11a was observed at doses of hu1124 between 0.01 and 0.1 mg/kg (group I). This pharmacodynamic response was accompanied by decreased numbers of epidermal and dermal CD3(+) T cells, decreased keratinocyte and blood vessel expression of ICAM-1, and epidermal thinning. Statistically significant drops in PASI compared with baseline were observed in group II patients at weeks 3 and 4 and in group III patients at weeks 2 through 10. No significant drop in PASI score was observed in group 1. Adverse events were mild at doses of 0.3 mg/kg or less and included mild chills, abdominal discomfort, headache, and fever. At a single dose of 0.6 mg/kg or higher, headache was the most common dose-limiting toxicity observed. CONCLUSION: Targeting CD11a may improve psoriasis by inhibiting T-cell activation, T-cell emigration into the skin, and cytotoxic T-cell function.     

银屑病患者血清中可溶性选择素E水平与疾病严重程度分析

应用ELISA法测定寻常型银屑病患者治疗前(31例),治疗后(30例)和正常人(20名)血清中可溶性选择素E水平。结果显示治疗前银屑病患者血清中可溶性选择素E水平显著高于正常人(t=3.277,P<0.005),并且与疾病严重程度(PASI记分)呈正相关(r="0.495,P<"0.005)。治疗后随病情好转,可溶性选择素E水平显著下降(t="3.119,P<"0.005),此下降现象在原PASI相对较高的患者中表现得更为明显。本文结果表明,血清中可溶性选择素E水平与寻常型银屑病患者病情相关,可作为判定银屑病活动性的一个有用指标。     

Our experience with etanercept in the treatment of psoriasis

Psoriasis is a chronic inflammatory disorder that usually requires long-term control. Etanercept has been shown to be effective in this disease. The efficacy and safety of etanercept were assessed in patients with psoriasis. In this 16-week open clinical trial, 29 patients with clinically stable psoriasis and psoriatic arthritis received etanercept (25 mg twice weekly) subcutaneously. All patients were evaluated for the psoriasis area, severity index (PASI) and Ritchie's articular index (RAI) which measures arthritis disease activity. Improvement by 75 percent in PASI, considered significant for psoriasis remission, was observed in nearly sixty percent of patients after 12-week etanercept therapy. The percentage of PASI improvement was nearly 25% at two weeks, 52.3% at four weeks and 78% at 12 weeks of etanercept treatment, and was maintained for the next four weeks. Comparable results were obtained in the improvement of psoriatic arthritis symptoms, as improvement of 75 percent in RAI was observed in 58.3 percent of patients after 12 weeks of etanercept therapy. The percentage of RAI improvement was nearly 26% at two weeks, 40.5% at four weeks and 73.6% at 12 weeks and 77.1% at 16 weeks of etanercept treatment. Etanercept was generally well tolerated, as most events were of mild severity. The treatment with etanercept led to significant improvement in patients with psoriasis over a period of 16 weeks.     

Prolonged cyclosporine treatment of severe or recalcitrant psoriasis: descriptive study in a series of 20 patients

Background  Although long‐term cyclosporine administration may induce toxic effects, it may be the only option for the treatment of severe psoriasis. The objective of the present study was to retrospectively evaluate efficacy and safety of long‐term cyclosporine treatment in a cohort of patients affected with moderate to severe psoriasis, recalcitrant or unresponsive to other treatments. Possible risk factors predicting an intolerance to cyclosporine were also investigated. Materials and methods  Data were collected on psoriatic patients treated with cyclosporine for at least six months at our Psoriasis Outpatient Unit between January 2005 and September 2010. The primary measure for clinical efficacy was the PASI 75 response. Cyclosporine safety was assessed through the review of both laboratory tests and the adverse events registered during the treatment. Results  Twenty patients affected with plaque or erythrodermic psoriasis were evaluated. At Week 16, the PASI 75 response was achieved by 85% of patients. Adverse events occurred in eight patients (40%): four experienced an increase in serum creatinine levels to more than 30% of their pre‐treatment values and four developed hypertension. Among these patients, five discontinued cyclosporine. Side effects resolved after stopping treatment. Conclusions  Our findings suggest that long‐term cyclosporine regimen can be justified in severe psoriasis not responsive to other treatments. When cyclosporine administration is required, obesity, pre‐treatment controlled hypertension, increased age (>70 years), and metabolic syndrome should be taken into consideration, as a significant correlation with occurrence of cyclosporine‐induced side effects has been found.     

T-cell activation is potentiated by cytokines released by lesional psoriatic, but not normal, epidermis.

BACKGROUND AND DESIGN--T-cell activation appears to be critical for the maintenance of psoriatic lesions. In this study, we determined whether cytokines released by epidermal cells from psoriatic lesions are providing signals that result in propagation of intralesional T-cell activation. Supernatants were obtained from epidermal cell cultures derived from skin biopsy specimens of psoriatic patients and normal subjects. These supernatants were added to purified normal CD4+ T cells activated via T-cell receptor (immobilized anti-CD3 and fibronectin) or via other activating pathways (anti-CDw60 or UM4D4). RESULTS--Psoriatic supernatants (n = 9), but not normal supernatants (n = 7, P < .0006), potentiated T-cell stimulation with anti-CD3 and fibronectin to 172% +/- 41% over control stimulation levels. The degree of lesional psoriatic epidermal cell potentiation correlated with the clinical severity of the lesion (r = .82, P = .007). Psoriatic epidermal cytokine potentiation of T-cell activation was not limited to T-cell receptor mediated stimulation; potentiation of anti-CDw60-stimulated CD4+ T cells was also observed. Neutralizing antisera to interleukin 1 and interleukin 8, but not interleukin 6, were found to reduce only partly the observed potentiation of T-cell activation. To determine whether cyclosporine is down modulating T-cell-potentiating cytokine activity in psoriasis, we compared samples obtained during a double-blind clinical trial of intralesional cyclosporine. T-cell-potentiating activity from psoriatic lesional sites treated with cyclosporine was not significantly modulated relative to the activity derived from vehicle-treated or untreated sites. CONCLUSION--These data demonstrate that lesional psoriatic epidermal cells release a balance of cytokines that potentiate T-cell activation. Because normal epidermal cells do not potentiate T-cell activation in this system, these findings demonstrate a mechanism by which the epidermis may non-specifically potentiate and perpetuate T-cell activation in psoriatic lesions.