银屑病患者外周血Th17/Th22细胞的表达

目的:检测寻常性银屑病(PV)患者外周血Th17、 Th22的水平及相关因子IL-17、IL-22 、IL-6的血清水平。方法: PASI评分评估患者病情,采用流式细胞术检测40例PV患者和30例健康对照者外周血Th17和Th22细胞,ELISA法检测血清中IL-17、IL-22和IL-6水平。结果: PV患者Th17细胞及Th22细胞,血清IL-17、IL-22及血清IL-6的水平明显高于健康对照组比较（P均<0.01）,且与PASI呈正相关（P＜0.05）。结论:Th17和Th22可能参与银屑病的发病。     

Kinetics of circulating Th17 cytokines and adipokines in psoriasis patients

Psoriasis is associated with an increase of Th17 cytokines, such as IL-17, IL-22, IL-21, and TNF-α, which are produced by Th17 cells. Adipokines are peptide hormones or cytokines secreted from adipose tissues and involved in the pathogenesis of metabolic syndrome (MS). Psoriasis patients have a high prevalence of the MS. In this study, we investigated the statistics of circulating Th17-related cytokines and adipokines in psoriasis patients. Our study identified the significant elevation of serum IL-6, IL-21, IL-22, and resistin levels in psoriasis patients. Increased serum levels of IL-22 and adiponectin were positively correlated with Psoriasis Area and Severity Index (PASI). In contrast, serum high molecular weight adiponectin levels were decreased in psoriasis and negatively correlated with PASI.     

窄谱中波紫外线治疗对寻常型银屑病Th22细胞及其相关细胞因子表达的影响

目的:观察窄谱中波紫外线(NB-UVB)治疗寻常型银屑病的疗效以及对寻常型银屑病患者Th22细胞及相关细胞因子的影响,探讨NB-UVB治疗银屑病的作用机制。方法:40例寻常型银屑病患者NB-UVB治疗20次,以皮损面积和严重程度(PASI)评分评价疗效;取患者治疗前后的外周血,用三色法流式细胞仪检测Th22细胞,ELISA法检测IL-6及IL-22的水平,并与健康对照组进行比较。结果:NB-UVB治疗后PASI评分明显下降(P0.01);银屑病患者治疗前外周血Th22、IL-6及IL-22的水平较对照组均明显增高(P0.01)。治疗后外周血Th22细胞的百分比(1.19±0.31)%,血清IL-6的水平(15.27±1.66)pg/mL及IL-22的水平(38.52±3.31)pg/mL较治疗前均明显下降(P值均0.01),且三者水平高低均与PASI呈正相关(P值均0.05)。结论:NB-UVB可能通过影响Th22细胞及IL-6、IL-22细胞因子来发挥治疗银屑病的作用。     

A comparison of serum inflammatory cytokines according to phenotype in patients with psoriasis

Summary Background Plaque-type psoriasis manifests with various morphological phenotypes and different clinical activity over time in the same individual or from one patient to another. Circulating cytokines, especially T-helper (Th) 1- and Th17-related, have been suggested to reflect the inflammatory nature of psoriasis. However, studies regarding cytokine profile according to morphological phenotypes are quite scarce. Objectives We sought to analyse the circulating Th1 and Th17 cytokines according to clinical phenotype and investigated the correlation between disease severity [Psoriasis Area and Severity Index (PASI)] and the serum level of inflammatory cytokines. Methods Seventy-one patients with psoriasis were divided into two groups according to clinical phenotype: chronic stable (CS) and eruptive inflammatory (EI). Th1- and Th17-derived cytokines were measured using multiplex cytokine assay. Results It was noted that interleukin (IL)-1 receptor antagonist and IL-17A were elevated in the EI group compared with the CS group. We also noticed that the PASI is relatively well correlated with serum cytokine level in the CS state but not as well in the EI counterpart. Conclusions The level of serum inflammatory cytokines differs according to morphological phenotype. Also, the PASI does not seem to be a suitable tool to assess disease severity in patients with psoriasis with EI characteristics.     

白芍总苷对轻、中度寻常性银屑病患者血清中IL-17和IL-23的影响

目的通过检测白芍总苷(TGP)治疗前后寻常性银屑病(PV)患者血清中Th17细胞的相关细胞因子IL~17和IL-23水平,探讨TGP治疗寻常性银屑病的可能作用机制。方法采用双抗体夹心酶联免疫吸附法(ELISA)检测30例PV患者经TGP治疗前后及20例健康对照组外周血清中IL-17和IL-23水平的改变,并分析这两种炎症因子在治疗前、后与PASI评分的相关性。结果治疗前PV患者血清IL-17和IL-23水平均较健康对照组显著升高(P<0.05);TGP治疗后血清中IL-17和IL-23水平均较治疗前显著降低(P<0.05);治疗前、后患者血清IL-17和IL-23水平与PASI评分均呈正相关(P均<0.05)。结论 TGP可能通过调节Th17细胞相关细胞因子IL-17和IL-23发挥治疗银屑病的作用。     

Effect of methotrexate on serum levels of IL-22 in patients with psoriasis

Interleukin-22 (IL-22) is the effector molecule of T-helper subset 22 (Th-22) lineage that promotes keratinocyte proliferation and dermal inflammation in psoriasis. Methotrexate is widely used as a first-line treatment in moderate to severe psoriasis. Methotrexate inhibits inflammatory and cytokinetic processes via various mechanisms, but the relevance of these to psoriasis is limited and whether methotrexate is specifically able to down-regulate Th22 cytokines is unknown. To determine if methotrexate reduces IL-22 in cases of psoriasis. Nineteen patients with moderate to severe psoriasis were given methotrexate 15 mg per week for up to 12 weeks. Serum levels of IL-22 were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment. Eleven of 19 patients (57.8%) achieved a 75% PASI score reduction. IL-22 levels were significantly higher in untreated psoriasis patients (56.63 ± 60.73 pg/mL) than in controls (12.58 ± 12.59 pg/mL). Methotrexate significantly reduced serum levels of IL-22 in psoriasis patients to 5.91 ± 7.97 pg/mL (p<0.001). Moreover, there was a significant positive correlation between IL-22 levels and PASI (r=0.63, p=0.004). Methotrexate significantly reduces serum IL-22 levels in cases of psoriasis. This is a novel mechanism by which methotrexate acts in the treatment of this disease.     

寻常性银屑病患者外周血Th17/Treg失衡的研究

目的 探讨寻常性银屑病患者外周血辅助性T细胞17（Th17）/调节性T细胞（Treg）的失衡及意义。方法 收集48例寻常性银屑病患者外周血,同时以PASI评分评价银屑病的严重程度,流式细胞仪检测48例寻常性银屑病患者和32例正常人外周血Th17、Treg细胞比例, ELISA方法检测患者和正常人血清中IL-17、IL-10表达水平。结果 寻常性银屑病患者外周血Th17细胞比例和血清IL-17水平分别为（2.70 ± 1.43）%和（90.65 ± 29.61） ng/L,较正常人组（0.86 ± 0.25）%和（48.82 ± 5.49） ng/L显著升高,差异有统计学意义（P值均 < 0.01）。Treg细胞比例和血清IL-10水平分别为（3.63 ± 1.14）%和（17.78 ± 4.09） ng/L,较正常人组（7.87 ± 1.26）%和（23.76 ± 3.82） ng/L显著下降,差异有统计学意义（P值均 < 0.01）。Th17/Treg和IL-17/IL-10比值分别为0.95 ± 0.76和5.78 ± 3.19,较正常人组（0.12 ± 0.06）和（2.16 ± 0.68）显著升高,差异有统计学意义（P值均 < 0.01）。银屑病患者PASI评分与Th17细胞比例、血清IL-17水平、Th17/Treg细胞和IL-17/IL-10比值呈正相关性（r值分别为0.97、0.93、0.99、0.97,P值均 < 0.01）,而与外周血Treg细胞比例和血清IL-10水平均呈负相关性（r值分别为-0.87、-0.90,P值均 < 0.01）。结论Th17/Treg失衡可能在寻常性银屑病的发病机制中具有一定作用。     

Serum and tissue levels of IL-17 in different clinical subtypes of psoriasis

Serum IL-17 levels and IL-17 mRNA expression have been reported to be higher in psoriatic skin than normal skin. There are very limited data in the literature about difference in the levels of this cytokine in various clinical disease subtypes. We aimed to evaluate whether there is a difference in the level of this cytokine according to clinical subtypes of psoriasis. 70 psoriasis patients (30 plaque psoriasis, 20 guttate psoriasis, and 20 pustular psoriasis) and 50 age- and sex-matched healthy volunteers were included in the study. Serum IL-17 levels were determined by ELISA. Skin biopsies obtained from lesions and non-lesional skin area of 12 patients and healthy individuals (n = 5) were analyzed by quantitative PCR (qPCR) to measure the mRNA levels of IL-17. Statistically, the serum IL-17 levels did not exhibit any difference between the patients and control groups. However, analysis of each subgroup revealed that the IL-17 levels were significantly higher in pustular psoriasis group (10.09 ± 12.6 pg/ml) than controls (4.4 ± 4.1 pg/ml) (p = 0.02). In addition, the IL-17 levels of plaque psoriasis patients with PASI score ≥10 (11.30 ± 6.0 pg/ml) were significantly higher than that of patients with PASI score <10 (3.39 ± 2.6 pg/ml) and controls (p < 0.001). The Pearson correlation analysis showed a positive correlation between the serum IL-17 levels and PASI. Lesional skin samples of psoriasis patients showed significantly higher levels of IL-17 mRNA compared with perilesional skin samples (p = 0.017). Also, in the pustular psoriasis, IL-17 mRNA levels were found to be distinctively high in comparison with other clinical subtypes and healthy controls. Our results indicate that IL-17 and Th17 cells have an important role in pustular psoriasis and severe psoriasis.     

消银合剂治疗血热证银屑病疗效及血清干扰素-γ、白介素-10检测

目的观察消银合剂对寻常性银屑病进行期血热证的临床疗效，并探讨其对银屑病Th1／Th2漂移的影响。方法选择寻常性银屑病进行期血热证患者60例，随机分为治疗组30例和对照组30例。治疗组给予消银合剂，对照组给予复方青黛胶囊，疗程8周。观察治疗前后PASI评分的变化，并测定30例治疗组患者治疗前后及20例正常对照者血清干扰素（INF）-γ、白介素（IL）-10水平。结果①治疗8周后，两组PASI积分均明显下降，治疗组PASI积分明显低于对照组（P〈0．05）。②治疗组有效率96．66％，优于对照组86．67％（P〈0．05）。③与正常对照相比，患者组INF-γ水平及INF-γ／IL-10比值明显升高，IL-10水平明显降低（P〈0．001）。治疗前PASI评分与血清INF-γ、IL-10水平均呈正相关（r=0．7，P〈0．001；r=0．43，P〈0．02）。治疗8周后，患者组血清INF-γ、IL-10水平，INF-γ/IL-10与健康对照组相比，无明显差异（P〉0．05）。结论消银合剂可能通过调节患者异常的INF-γ、IL-10水平而治疗银屑病。     

甲氨蝶呤对中重度斑块型银屑病患者T细胞相关细胞因子表达水平的影响

 目的:探讨甲氨蝶呤（MTX）治疗中重度斑块型银屑病16周后，应答组和未应答组外周血T细胞相关细胞因子IFN-γ、IL-4、IL-17a、IL-21及TGF-β表达水平的变化。方法：纳入采用MTX系统性治疗16周后的中重度斑块型银屑病患者作为研究对象,其中应答组49例、未应答组13例、健康对照组35例，分析并比较62例银屑病患者治疗前后、应答组和未应答组治疗后生化指标及外周血IFN-γ、IL-4、IL-17a、IL-21、TGF-β表达水平的差异，采用Pearson相关分析银屑病患者治疗前PASI评分与血清IFN-γ、IL-4、IL-17a、IL-21、TGF-β表达水平的相关性。结果:银屑病患者治疗16周后血清肌酐、尿酸、尿素氮、ALT及AST较治疗前明显升高（P值均＜0.05），而应答组与未应答组所有生化指标相比较无明显差异。应答组治疗后血清IFN-γ［（749.03±76.77) pg/mL vs (953.69±101.58） pg/mL］、IL-17a［（756.96±101.73) pg/mL vs (963.75±64.38) pg/mL］、IL-21［（514.76±53.48) pg/mL vs (693.45±87.91) pg/mL］较治疗前明显降低（P值均＜0.05），TGF-β［（433.59±65.39) pg/mL vs (298.36±77.83) pg/mL］较治疗前明显升高（P＜0.05），而IL-4［（218.72±67.39) pg/mL vs (198.78±47.71) pg/ mL］较治疗前无明显差异；未应答组治疗前后所有细胞因子相比较均无明显差异（P值均＞0.05）。Pearson相关分析结果显示，治疗前患者PASI评分与IFN-γ、IL-17a、IL-21、TGF-β水平均存在明显相关（r值分别为0.25、0.75、0.66、-0.11，P值均＜0.05)。结论:MTX治疗银屑病的潜在机制可能与改善Th1/Th2、Th17/Treg细胞免疫失衡有关。     

Squamous cell carcinoma-related antigen (SCCr-Ag), sICAM-1 and beta 2-microglobulin are useful markers of disease activity in psoriasis

Several published studies suggest the involvement of immune and inflammatory factors in psoriasis. We recently demonstrated that the number of circulating ICAM-1 + lymphocytes and the levels beta 2-microglobulin are useful parameters in monitoring the activity of the disease. In this study we investigated serum levels of SCCr-Ag in 24 patients with psoriasis in order to determine whether this antigen is a marker of disease activity. Our results demonstrated high serum levels of SCCr-Ag, IL-2, sIL-2R, sCD4, sCD8, sICAM-1 and beta 2-microglobulin in the acute phase of psoriasis. Furthermore, we found a positive correlation of SCC with TBSA, PASI score, sICAM-1 and beta 2-microglobulin. These data demonstrate that serum levels of SCCr-Ag depend on the severity of the disease and correlate with both immunological and inflammatory markers of disease activity. We suggest that expression of SCCr-Ag may be induced by cytokines in the microenvironment of psoriatic lesions, suggesting that SCC-Ag may play a role in the inflammatory process.     

Soluble tumor necrosis factor alpha receptor type 1 in psoriasis patients treated with narrowband ultraviolet B

PURPOSE: The purpose of this study was to examine the influence of narrowband ultraviolet (NB-UVB) therapy on the serum concentration of soluble tumor necrosis factor receptor type 1 (sTNF-R1) in psoriasis patients. METHODS: Twenty-seven patients received NB-UVB therapy three to five times a week for 4 weeks. The assessment of skin lesions using psoriasis area and severity index (PASI) and serum concentration of sTNF-R1 was performed at the baseline, at 2, 4 and 4 weeks after treatment cessation. The sera of healthy subject were used as controls. RESULTS: The baseline PASI was 13.56 +/- 5.71, sTNF-R1 concentration was 1.89 +/- 0.43 ng/ml in patients and 1.48 +/- 0.30 ng/ml in controls (P < 0.05). The baseline PASI correlated to sTNF-R1 (r = 0.52, P < 0.05). The decline in concentrations of sTNF-R1 paralleled the decline of PASI achieved during therapy but still exceeded control values. CONCLUSION: The results of the study confirm the role of sTNF-R1 as a marker of psoriasis severity and efficacy of treatment. They also suggest that NB-UVB influences the serum level of sTNF-R1.     

Increased interleukin-7 levels in the sera of psoriatic patients: lack of correlations with interleukin-6 levels and disease intensity

Interleukin (IL)-7 is a multifunctional cytokine which is involved in the regulation of keratinocyte-T lymphocyte interactions; the latter is an important factor in the pathogenesis of psoriasis. In vitro, IL-7 is able to induce release of cytokines, including IL-6; IL-6 expression is known to be enhanced in psoriatic patients. Serum levels of IL-7 and IL-6 were measured by ELISA in 40 psoriatic patients and compared with cytokine levels in 18 healthy individuals. Serum levels of IL-7 were also evaluated in 24 psoriatic patients during the remission of the disease after effective treatment. The IL-7 and IL-6 serum levels were significantly higher in psoriatic patients than in healthy subjects and the IL-7 serum levels did not significantly decrease after treatment. Serum levels of IL-7 did not correlate with PASI scores; however, a significant positive relationship was observed between IL-6 levels and PASI scores. There was no correlation between increased levels of IL-7 and IL-6 in the sera of psoriatic patients, suggesting the lack of a direct link between these two cytokines in the psoriatic process. In conclusion, increased IL-7 serum levels suggest that IL-7, like IL-6, may be involved in the pathogenesis of psoriasis, but in contrast with IL-6, serum IL-7 levels could not be used as a marker of disease activity in psoriatic patients.     

阿维A对银屑病患者血清STCP-1,GM-CSF的影响

目的观察阿维A治疗银屑病的疗效及对银屑病患者血清中细胞因子水平的影响。方法分别用酶联免疫吸附法和放射免疫吸附法检测寻常性银屑病各期患者服用阿维A胶囊治疗前后血清STCP-1和GM-CSF的水平并进行PASI评分。结果阿维A治疗寻常性银屑病后治愈11例(31.43%),有效率为82.85%。银屑病患者在治疗前血清STCP-1和GM-CSF的水平均比健康对照组显著升高(P(0.01),同时发现治疗前进行期患者细胞因子水平比静止期高(P(0.01);阿维A治疗后血清STCP-1和GM-CSF水平均显著下降(P(0.05,P(0.01)。患者血清GM-CSF水平与PASI评分呈正相关(r=0.421,P(0.05),STCP-1水平与PASI评分无相关性(r=0.244,P(0.05)。结论阿维A对寻常性银屑病患者有较好的治疗作用,血清STCP-1和GM-CSF在银屑病的发病中有重要意义。     

Soluble intercellular adhesion molecule-1 levels in patients with psoriasis

A newly developed ELISA was used to detect and quantify the presence of a soluble form of intercellular adhesion molecule-1 (sICAM-1) in the circulation of healthy individuals compared with patients with psoriasis vulgaris. Seventeen psoriatic patients were studied. The extent of skin lesions was rated by the psoriasis area and severity index (PASI). Seventeen age- and sex-matched healthy individuals served as controls. Serum levels were measured by an ELISA technique utilizing an anti-ICAM-1 murine monoclonal antibody bound to the solid phase, and a second, peroxidase-conjugated monoclonal antibody reacting with sICAM-1. Serum levels in controls were 358.8±87.9 ng/ml sICAM-1, and 480.5±133.6 ng/ml in psoriatics (mean±SD; P=0.02). In psoriasis. sICAM-1 levels were found to be directly proportional to the PASI score (y=363.002 + 8.525x, R=0.55. P=0.021). These data suggest that the concentration of sICAM-1 in serum increases during psoriatic inflammation. The origin and function of sICAM-1 in psoriasis remain to be defined.     

走罐联合消疕2号方治疗血瘀型斑块状银屑病临床疗效及对相关细胞因子的影响

目的 观察走罐疗法联合消疕2号方治疗血瘀证斑块状银屑病的有效性、安全性及对辅助性T细胞(Th17)细胞因子的影响.方法 60例斑块状银屑病(血瘀证)患者作为研究对象,随机分为治疗组30例和对照组30例.对照组内服消疕2号方治疗,治疗组在对照组的基础上加用走罐疗法.比较2组患者治疗前后银屑病皮损面积及严重程度指数(PAS...     

不同证候银屑病患者外周血Th1/Th17细胞表达差异的研究

目的 探讨不同证候银屑病的发病与外周血Th1/Th17细胞轴漂移的相关性。方法 用流式细胞仪检测CD4+T细胞内细胞因子干扰素?酌（IFN-?酌）、白介素17A（IL-17A）的表达情况,双抗体夹心法（ELISA）检测不同证候银屑病患者血清中Th１型细胞因子IFN-?酌和Th17型细胞因子IL-17A的水平。 结果 血热组银屑病患者外周血单一核细胞（PBMC）中CD4+IFN-?酌+水平显著高于血瘀组及健康对照组（P < 0.05）,而血瘀组与健康对照组外周血PBMC中CD4+IFN-?酌+水平差异无统计学意义。血热组银屑病患者PBMC中CD4+IFN-?酌+水平与PASI评分呈正相关（P < 0.05）,血瘀组不具相关性（P > 0.05）。血热组、血瘀组银屑病患者及健康对照组PBMC中CD4+IL-17A+三组间差异无统计学意义。血热组银屑病患者PBMC中CD4+IL-17A+水平与PASI评分不具相关性（P > 0.05）,而血瘀组呈正相关（P < 0.05）。ELISA结果示,血热组银屑病患者外周血清中IFN-?酌水平显著高于血瘀组及健康对照组（P < 0.05）,而血瘀组与健康对照组差异无统计学意义（P > 0.05）;血热组银屑病患者血浆中IFN-?酌水平与PASI评分呈正相关（P < 0.05）,血瘀组银屑病患者呈负相关（P < 0.05）。血热组、血瘀组银屑病患者及健康对照血清中IL-17A水平三组间差异无统计学意义（P > 0.05）,血热、血瘀组银屑病患者血清中IL-17A水平与PASI评分不具相关性（P > 0.05）。 结论 Th1细胞在血热型银屑病的发病中占主导地位,当血热型银屑病向血瘀型转化或正常转归时,Th1细胞的表达下降,而Th17细胞在不同证候银屑病患者中差异无统计学意义。     

寻常性银屑病患者外周血和皮损中Th17细胞及相关因子的表达

目的 探讨寻常性银屑病患者外周血和皮损中Th17细胞及相关因子IL-17、IL-22表达,分析其与疾病严重程度及病程的相关性。方法 抽取44例寻常性银屑病患者和28例正常人对照者外周血,用三色法流式细胞仪检测外周血Th17细胞,ELISA法检测血清中IL-17、IL-22表达。取20例寻常性银屑病患者皮损和8例正常人对照者皮肤,用量子点免疫荧光双标法检测Th17细胞表达。结果 寻常性银屑病患者外周血Th17细胞百分比（4.71% ± 2.55%）高于正常人对照组（0.55% ± 0.39%）,两组差异有统计学意义（P < 0.01）。银屑病患者Th17细胞与银屑病病情严重度评分（PASI）呈显著正相关（r = 0.53,P < 0.01）,但与病程无相关性（r = 0.09,P > 0.05）。银屑病患者血清中IL-17（24.02 ± 12.31 ng/L）、IL-22（18.32 ± 8.14 ng/L）表达均高于正常人对照组（IL-17为7.16 ± 4.04 ng/L,IL-22为6.52 ± 4.15 ng/L）,差异均有统计学意义（P < 0.01和 < 0.05）。银屑病患者血清IL-17、IL-22表达与PASI呈显著正相关（r = 0.47,P < 0.01;r = 0.53,P < 0.01）,与病程无相关性（r = 0.03,P > 0.05;r = 0.19,P > 0.05）。银屑病患者皮损中可见Th17细胞浸润,主要集中在真皮浅层血管周围;而正常人皮肤中仅有微量CD4+ T细胞表达,未见Th17细胞。 结论 Th17细胞参与银屑病的发病,提示阻断相关因子IL-17、IL-22的药物可成为治疗银屑病的又一新靶点。     

窄谱中波紫外线治疗寻常性银屑病患者疗效观察及白细胞介素6和17的检测

目的 探讨窄谱中波紫外线(NB-UVB)对寻常性银屑病患者血清中白细胞介素(IL)6和17的影响.方法 40例银屑病患者用NB-UVB照射治疗,每周3次,共治疗6周,分别于光疗前、光疗9次和光疗18次后,测定患者治疗前后血清IL-6和IL-17的水平,并以40例健康人作对照.结果 患者NB-UVB治疗前PASI评分15.68±2.86,光疗9次为10.58±1.36,光疗18次后为3.08±1.37,治疗前后评分对照,差异有统计学意义(P＜0.01).银屑病患者NB-UVB照射治疗前后,IL-6水平分别为(61.82±15.61)pg/L和(20.43±9.78)pg/L,差异有统计学意义(P＜0.05).IL-17水平分别为(41.56±10.34) pg/L和(26.32±7.24)pg/L,差异有统计学意义(P＜0.05).健康人血清IL-6和IL-17水平分别为(1.50±1.82) pg/L和(13.47±2.15)pg/L,健康人之间差异无统计学意义(P＞0.05).40例银屑病患者中,治愈20例,显效15例,有效率为87.5％.结论 NB-UVB照射可提高银屑病的疗效,并降低外周血IL-6、IL-17的水平.