Borrelia burgdorferi potently activates bone marrow-derived conventional dendritic cells for production of IL-23 required for IL-17 release by T cells

Lyme borreliosis is characterized by cellular inflammatory responses at multiple body sites. Recently, an association of interleukin-17 (IL-17) and Lyme arthritis was suggested. In this context, it is of special interest that the heterodimeric cytokine IL-23 can act on T cells and initiate the up-regulation of effector cytokines such as IL-17. To determine the role of this specific cytokine cascade for the induction of subsequently induced proinflammatory events we developed an in vitro system to investigate the IL-23-inducing capacity of Borrelia burgdorferi and the potential of the spirochete for inducing the IL-23/IL-17 axis. We used cells derived from mice deficient for IL-23 or IL-12 only or deficient for both IL-12 and IL-23 to define precisely the function of these cytokines. Experiments with bone marrow-derived dendritic cells (BMDC) identified these cells as sources for IL-23 but not for IL-12 after B. burgdorferi exposure. Subsequent investigations with T cell-depleted splenocyte fractions revealed a tight IL-23/IL-17 axis in response to the spirochetes. Monoclonal antibodies that block IL-23 showed further that BMDC-derived IL-23 was required for production of IL-17 in this experimental model. These in vitro data describing a spirochete-induced release of IL-23 may help to define IL-17-dependent inflammatory responses in the disease.     

Homogeneity of Borrelia japonica and heterogeneity of Borrelia afzelii and 'Borrelia tanukii' isolated in Japan, determined from ospC gene sequences

Borrelia afzelii, B. japonica, and `B. tanukii' isolated from various sources and geographical origins in Japan were characterized by restriction fragment length polymorphism (RFLP) analysis and sequencing analysis of the outer surface protein C (OspC) amplicon. B. afzelii and `B. tanukii' generated variable RFLP patterns and differences in ospC gene sequence were confirmed. In contrast, 26 isolates of B. japonica generated one OspC RFLP type, and sequence similarity between B. japonica ranged from 96.4 to 99.7%. These finding suggests that B. japonica is unique in comparison with other members of B. burgdorferi sensu lato species with respect to homogeneity of the ospC gene.     

Cyclooxygenase 2 activity modulates the severity of murine Lyme arthritis

Cyclooxygenase (Cox) is a key enzyme in the biosynthetic metabolism of prostaglandins. The inducible isoform of Cox-2 has been implicated in inflammation and its specific inhibition can be used to treat noninfectious inflammatory diseases, such as rheumatoid arthritis. Borrelia burgdorferi, the agent of Lyme disease, can induce joint inflammation. Here we show that B. burgdorferi induced the upregulation of cox-2 gene expression in murine joints at the onset of arthritis in infected mice. The level of mRNA expression correlated with the degree of inflammation. The specific inhibition of Cox-2 diminished the degree of joint inflammation, without affecting B. burgdorferi-specific antibody or cytokine responses. Cox-2 activity is therefore associated with the genesis of infectious arthritis caused by B. burgdorferi.     

Levels of serum pentraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis

ObjectiveThe aim of this study was to investigate the relationship between disease severity and biochemical parameters such as pentraxin-3, fetuin-A, IL-6, insulin and HOMA-IR levels in patients with rheumatoid arthritis.MethodsThis study included 60 patients with RA and 20 healthy controls. Serum pentraxin-3, fetuin-A, IL-6 and insulin concentrations were measured. Also, HOMA-IR values were calculated. Disease activity was assessed with Disease Activity Score (DAS28). To evaluate quality of life, the Health Assessment Questionnaire disability index was applied.ResultsThe serum values for ESR, CRP, pentraxin-3 and fetuin-A in patients with RA were found to be higher than control subjects (p values = 0.001, 0.001, 0.000, 0.000, 0.01, 0.02, respectively). A positive correlation was evident between the DAS 28 score and IL6 levels (r = 0.263, p = 0.045). We found no correlation between the DAS28 score and HOMA-IR, the levels of pentraxin 3, fetuin A, insulin (p < 0.05). Fetuin A levels were positively correlated with cumulative steroid dose (r = 0.382, p = 0.035). A statistically significant correlation was evident between presence of cardiovascular disease and HOMA-IR values in RA patients (r = 0.437, p = 0.032).ConclusionElevated levels of pentraxin-3, fetuin-A, CRP, ESR might play a role in the pathogenesis of RA. Levels of fetuin-A, insulin HOMA-IR, pentraxin-3, CRP and ESR were not associated with clinical severity of the RA.     

Animal and human antibodies reactive with the outer surface protein A and B of Borrelia burgdorferi are borreliacidal, in vitro, in the presence of complement

Abstract Polyspecific antibodies present in ascitic fluids of mice (pMIAFs) immunized with whole Borrelia burgdorferi cells exerted borreliacidal activity in vitro when tested with complement and homologous antigen but not with heterologous B. hermsii . Similarly, monospecific mouse antibodies obtained by immunizing mice with purified preparations of outer surface protein A and B of B. burgdorferi were borreliacidal. On the contrary, mouse monospecific antibodies raised against the 41-kDa flagellar protein of B. burgdorferi did not kill borreliae in the presence of complement. A complement-mediated, in vitro, borreliacidal activity was observed in human sera from patients with Lyme disease when antibodies against OspA and/or OspB were detectable in sera by the Western blotting technique. The in vitro borreliacidal activity of human sera was evident after 14 h incubation with live B. burgdorferi spirochaetes and complement, whereas antibodies present in mouse immune ascitic fluids killed borreliae after 1 h incubation.     

Expression of Endothelial Cell Adhesion Molecules in Joints and Heart during Borrelia burgdorferi Infection of Mice

The expression of adhesion molecules on endothelia was examined during chronic arthritis and carditis in SCID and immunocompetent susceptible AKR/N mice infected with Borrelia burgdorferi (B. burgdorferi). All stages of disease were associated with the upregulation or new expression of ICAM-1 and P-selectin and of VCAM-1 and E-selectin, respectively, on blood vessels of affected joint tissues of SCID and AKR/N mice as well as on heart tissue of SCID mice but not in other tissues. Moreover, ICAM-1 was also found on infiltrating mononuclear cells. The overall staining intensity for each of the four adhesion molecules on individual tissue sections of joint and heart increased with time of infection and was associated with the presence of spirochetes in the tissue. In addition it is shown that in both mouse strains inflammation of joints but not heart is accompanied by vascular proliferation. Synovial but not heart tissues of infected SCID mice were found to express both, peripheral-(PNAd) and mucosal (MAdCAM-1) lymph node high endothelia venule associated vascular addressins as detected by mAb Meca-79 and Meca-367, respectively, but only at later stages of the disease and only on newly generated small venules. However, neither of the two addressins were evident in synovial lesions of AKR/N mice. Together the data suggest that the concomittant induction of ICAM-1, VCAM-1, E-selectin and P-selectin in lesions of infected mice provide a means for enhanced cellular infiltration into affected organs and that the regulation of these structures is conserved in the absence of a functional immune system. Furthermore, the differential induction of vascular proliferation in joint and heart tissues as well as the restricted expression patterns of vascular addressins indicate that the pathogenetic processes induced by B. burgdorferi are distinct for joint and heart.     

重组人白细胞介素15融合蛋白的表达、纯化及免疫原性检测

目的:以白细胞介素15(IL-15)为靶点,研制类风湿性关节炎免疫治疗蛋白疫苗。方法:将N端融合破伤风类毒素(TT)表位的人IL-15基因克隆至带有His标签的原核表达载体pQE-30上,转化大肠杆菌M15,经IPTG诱导表达,获得重组人TT-IL-15融合蛋白(简称rtIL-15);目的蛋白经镍柱亲和层析纯化后,用Western印迹和HPLC进行鉴定;将rtIL-15与氢氧化铝佐剂混合,免疫BALB/c小鼠,检测疫苗的免疫原性。结果:双酶切鉴定和核苷酸序列测定结果表明重组融合表达质粒pQE-30-TT-IL-15构建正确,重组蛋白的表达量达到菌体总蛋白的20%,主要以包涵体形式表达,经过纯化、复性后,目的蛋白纯度达到95%以上;蛋白疫苗免疫小鼠后,能诱导高滴度的特异性的IL-15抗体。结论:在大肠杆菌中表达了重组人IL-15融合蛋白疫苗,并具有良好的免疫原性。     

TAK1基因沉默对TNF-a诱导的滑膜细胞IL-6、IL-8表达的影响

目的：观察转化生长因子β激活激酶1（TAK1）基因沉默对肿瘤坏死因子a （TNF-a）诱导的滑膜细胞中促炎介质白介素-6（IL-6）和白介素-8（IL-8）表达的影响,以探讨TAK1在类风湿关节炎（RA）发病中的作用。方法：采取脂质体转染方法将TAK1特异性的小干扰RNA （siRNA）和阴性对照RNA （scRNA）导入类风湿关节炎的滑膜成纤维细胞株MH7A细胞,然后分别用20 ng/ml TNF-a刺激后,检测细胞内IL-6、IL-8 mRNA的表达和培养上清中IL-6和IL-8分泌情况以及p38、ERK、JNK、p65磷酸化的水平和抑制性蛋白IκBα的变化情况。结果：siRNA-TAK1转染72 h后滑膜细胞中TAK mRNA和蛋白表达的平均抑制率分别为75%和55%。siRNA-TAK1转染下调TNF-a诱导状态下IL-6和IL-8的表达,并能抑制p38、JNK、p65磷酸化和增加IκBα水平。结论：TAK1基因沉默能抑制TNF-a诱导的滑膜细胞IL-6、IL-8表达,可能与其抑制JNK和p38MAPK的活化及NF-κB的活化有关。     

Are genetic variations in IL-21–IL-23R–IL-17A cytokine axis involved in a pathogenic pathway of rheumatoid arthritis? Bayesian hierarchical meta-analysis

Inflammatory cytokines have been established to be involved in the pathogenesis of rheumatoid arthritis (RA). The genetic polymorphisms in the interleukin (IL) 23 receptor (IL23R), IL21, and IL17 have been associated with RA risk. However, there is no conclusive understanding of the genes encoding the immunoinflammatory IL-21–IL-23R–IL-17A pathway in RA aetiopathogenesis. This meta-analysis was conducted to attain this goal. A comprehensive literature search was conducted in Scopus and PubMed to look for the relevant case–control studies up until 2018. A Bayesian hierarchical meta-analysis was carried out to assess the association between the polymorphisms and the risk of RA. The association was estimated by calculating the logarithm of odds ratio (Log OR) and 95% credible interval (95% CI). In this meta-analysis, 37 case–control studies comprising 23,506 RA patients and 25,984 healthy individuals were found for analyzing the IL23R, IL21, and IL1A gene polymorphism and risk of RA. In the IL23R gene rs1343151 SNP, the minor A allele significantly increased the risk of RA (Log OR = 0.085, 95% CI = 0.008, 0.156). Moreover, the minor AA genotype was significantly associated with increased RA risk (Log OR = 0.176, 95% CI = 0.028, 0.321). In addition, the C allele of the IL23R gene rs2201841 SNP significantly decreased the disease risk (Log OR = −0.544, 95% CI = −1.0, −0.065). Since Bayesian meta-analysis is a powerful strategy to pool the data, it can be mentioned that genetic polymorphisms of IL23R, but not IL21 and IL17A, are involved in susceptibility to RA.     

Relationship among nitric oxide, leptin, ACTH, corticosterone, and IL-1beta, in the early and late phases of adjuvant arthritis in male Long Evans rats

Leptin, a hormone regulating body weight, food intake, and metabolism, is associated with activation of immune cells and inflammation. In this study we analyzed levels of leptin, adrenocorticotropic hormone (ACTH), corticosterone, interleukin 1beta (IL-1beta), and nitric oxide (NO) production on days 10 and 22 of adjuvant arthritis (AA) in male Long Evans rats to ascertain possible relationship of leptin with its modulators during the early and late phases of chronic inflammation. The circulating leptin levels were significantly reduced already on day 10 of AA compared to controls (1.97+/-0.22 ng/ml vs. 3.08+/-0.25 ng/ml, p<0.05); on day 22 no significant further drop was observed (1.06+/-0.21 ng/ml). Leptin mRNA in epididymal fat tissue was reduced in arthritic animals compared to controls on day 22 (0.61+/-0.09 vs. 1.30+/-0.1 arbU/GAPDH (p<0.01). IL-1beta concentration in spleen was enhanced on day 10 of AA (24.55+/-4.67 pg/100 microg protein vs. 14.33+/-1.71 pg/100 microg protein; p<0.05); on day 22 it did not differ from controls. ACTH and corticosterone levels were significantly elevated only on day 22 of AA (ACTH: 306.17+/-42.22 pg/ml vs. 157.61+/-23.94 pg/ml; p<0.05; corticosterone: 5.24+/-1.38 microg/100 ml vs. 1.05+/-0.23 microg/100 ml; p<0.01). Nitrate levels were enhanced similarly on days 10 (49.86+/-1.83 microM) and 22 of AA (43.58+/-2.17 microM), compared to controls (23.42+/-1.39 microM, p<0.001). These results show that corticosterone does not stimulate leptin production during AA. The suppression of leptin may be a consequence of permanent activation of NO, IL-1beta, and of lower weight gain. Circulating leptin does not seem to play a key role in the progression of chronic arthritis.     

Detection of Borrelia burgdorferi and Anaplasma phagocytophilum in the black‐legged tick,Ixodes scapularis,within southwestern Pennsylvania

Prevalence studies of Borrelia burgdorferi and Anaplasma phagocytophilum have been rare for ticks from southwestern Pennsylvania. We collected 325 Ixodes scapularis ticks between 2011 and 2012 from four counties in southwestern Pennsylvania. We tested for the presence of Borrelia burgdorferi and Anaplasma phagocytophilum using PCR. Of the ticks collected from Pennsylvania, B. burgdorferi (causative agent of Lyme disease) was present in 114/325 (35%) and Anaplasma phagocytophilum (causative agent of Human Granulocytic Anaplasmosis) was present in 48/325 (15%) as determined by PCR analysis.     

Cytokine production by dendritic cells genetically engineered to express IL-4: induction of Th2 responses and differential regulation of IL-12 and IL-23 synthesis

Dendritic cells (DCs) retrovirally transduced with IL-4 have recently been shown to inhibit murine collagen-induced arthritis and associated Th1 immune responses in vivo, but the mechanisms that underly these effects are not yet understood. In this report we demonstrate that IL-4-transduced DCs loaded with antigen led to lower T cell production of IFN-gamma, increased production of IL-4, and an attenuated, delayed type hypersensitivity response. We hypothesized that the ability of such DCs to regulate the Th1 immune response in vivo depends in part on their capacity to produce IL-12 and IL-23. Quantitative mRNA analysis revealed that IL-4-transduced DCs stimulated with CD40 ligand expressed higher levels of IL-12p35 mRNA, but lower levels of mRNA for IL-23p19 and the common subunit p40 found in both IL-12 and IL-23, compared with control DCs. These results, which indicate that expression of the IL-12 and IL-23 subunits is differentially regulated in IL-4-transduced DCs, were confirmed by ELISA of the IL-12 and IL-23 heterodimers. Thus, therapeutic suppression of Th1 -mediated autoimmunity (as recently shown in murine collagen-induced arthritis) and induction of Th2 responses in vivo by IL-4-transduced DCs occurs despite their potential to produce increased levels of IL-12, but could reflect, in part, decreased production of IL-23.     

Co-expression of IL-18 binding protein and IL-4 regulates Th1/Th2 cytokine response in murine collagen-induced arthritis

We constructed a recombinant adenoviral vector containing a murine interleukin （IL）-18 binding protein （mlL-18BP） and murine IL-4 （mIL-4） fusion gene （AdmIL-18BP/mIL.4） and used a gene therapy approach to investigate the role of IL-18BP and IL-4 in modulating the T-helperl and T-helper2 （Th1/Th2） balance in mice with collagen-induced arthritis （CIA）. Mice with CIA were intra-articularly injected with 107 pfu/6 μl ofeitherAdmIL.18BP/mIL-4, or a controladenovirus, or with the control vehicle （phosphate-buffered saline）. After intra-articular gene therapy with AdmIL-18BP/mIL-4, the serum levels of tumor necrosis factor-α （TNF-α）, T-interferon （IFN-γ）, IL-4, IL-10, and IL-18 in mice with CIA were assessed by ELISA. IFN-T-expressing and IL-4-expressing CD4^＋ T cells from mice splenocytes were monitored by flow cytometry. Mice with CIA at weeks 1, 2, and 4 after intraarticular injection of AdmIL-18BP/mIL-4 showed significantly increased serum concentrations of IL-4 and IL-10 （P〈0.01 at all time points） but greatly decreased serum concentrations ofIFN-γ, TNF-α and IL-β （P〈0.01 at all time points ） compared to both the con trol adenovirus and phospha tebuffered saline control groups. The percentage of LFN-γ- producing CD4^＋ T cells was significantly decreased in response to local AdmIL-18BP/mIL-4 treatment. The percentage of IL-4-producing CD4^＋ T cells increased significantly at 1 week after local injection of AdmIL-18BP/ mIL-4 then returned to normal by week 4. These data indicated the significant modifying effects on the Th1/Th2 imbalance in murine CIA produced by local overexpression of IL-18BP and IL-4. Combination treatment with IL-18BP and IL-4 is a promising potential therapy for rheumatoid arthritis.     

艾拉莫德片联合双醋瑞因治疗类风湿关节炎的临床疗效及对患者血清IL-17、IL-23水平的影响

目的:探讨艾拉莫德片联合双醋瑞因治疗类风湿关节炎的临床疗效及对患者血清白介素(IL)-17、IL-23水平的影响。方法:选择2015年9月至2017年9月我院接诊的96例类风湿关节炎患者,通过随机数表法将其分为观察组(n=48)和对照组(n=48),两组均给予甲氨蝶呤片及常规对症治疗,对照组在此基础上给予艾拉莫德片治疗,观察组在对照组的基础上联合双醋瑞因胶囊治疗,两组均以4周为1个疗程,连续治疗6个疗程。比较两组的临床疗效、治疗前后临床症状评分、实验室指标[红细胞沉降率(ESR)、C反应蛋白(CRP)、类风湿因子(RF)]、免疫学指标[免疫球蛋白(Ig)G、IgA、IgM]及血清IL-17、IL-23水平的变化及治疗期间不良反应的发生情况。结果:治疗后,观察组临床疗效总有效率为89.58%(43/48),明显高于对照组的70.83%(34/48)(P0.05);两组关节疼痛、关节压痛、关节肿胀、晨僵时间评分、ESR、CRP、RF、IgG、IgA、IgM较治疗前均显著降低(P0.05),观察组以上指标均明显低于对照组(P0.05);两组血清IL-17、IL-23水平均较治疗前显著降低(P0.05),观察组血清IL-17、IL-23水平均明显低于对照组[(11.23±1.30)pg/ml vs(16.49±1.79)pg/mL,(83.41±10.25)pg/mL vs(103.52±12.47)pg/mL](P0.05)。两组治疗期间药物不良反应总发生率比较无显著差异(P0.05)。结论;艾拉莫德片联合双醋瑞因治疗类风湿关节炎患者的效果显著,可明显改善患者的临床症状,促进关节功能恢复,其内在机制可能和降低血清IL-17、IL-23的表达相关。     

IL-20: biological functions and clinical implications

Summary IL-20 belongs to the IL-10 family and plays a role in skin inflammation and the development of hematopoietic cells. Little is known about its other biological functions and clinical implications, however. Updated information about IL-20, such as its identification, expression, receptors, signaling, biological activities, and potential clinical implications, is illustrated in this review based on our research and on data available in the literature. Our studies of IL-20 show that it is a pleiotropic cytokine with potent inflammatory, angiogenic, and chemoattractive characteristics. Inflammation and angiogenesis are essential for the pathogenesis of rheumatoid arthritis and atherosclerosis. Based on in vitro data and clinical samples, we demonstrated that IL-20 is involved in the diseases of rheumatoid arthritis and atherosclerosis. In addition, we found in our studies that IL-20 signaled through different molecules in several cells. The present review presents the clinical implications of IL-20 in rheumatoid arthritis and atherosclerosis. It may provide new therapeutic options in the future.This work was supported by a grant from Chi-Mei Medical Center, Tainan, Taiwan.     

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.     

川芎嗪对类风湿性关节炎患者外周血IL-17 和Foxp3 的影响

目的:探究川芎嗪对类风湿性关节炎患者外周血IL-17、Foxp3的影响。方法:选取我院风湿科收治的类风湿性关节炎住院患者共60例,随机分为对照组30例,给予甲氨喋吟片与乐松片治疗,实验组30例,在对照组的基础上给予盐酸川芎嗪注射液,连续14 d。治疗期间观察患者有无不良反应,注意饮食,忌烟酒。治疗结束后,RT-PCR检测外周血RORTt、Foxp3 m RNA的表达;免疫组化检测外周血IL-17、Foxp3水平。结果:与治疗前相比,治疗后两组患者的RORTt水平明显降低,Foxp3水平明显增高,RORTt/Foxp3比值明显减小,治疗后,与对照组相比,RORTt、RORTt/Foxp3比值较低,Foxp3水平较高(P0.05);与治疗前相比,治疗后两组患者的IL-17水平降低,Foxp3水平均升高(P0.05),与对照组相比,上述指标改善更为明显(P0.05)。结论:川芎嗪对类风湿性关节炎明显下调外周血RORTt水平,降低IL-17,升高Foxp3水平,提高患者免疫功能,从而减轻炎症反应,改善患者临床症状及不良预后,临床值得推广应用。     

Characterization of Borrelia garinii isolated from Lyme disease patients in Hokkaido, Japan, by sequence analysis of OspA and OspB genes

The outer surface proteins OspA and OspB genes of clinical Borrelia garinii isolates (JEM1–8) from Hokkaido, Japan were sequenced. One strain, JEM4, has a single ospA gene which is similar to European B. garinii strains PBr (sequence homology value: 94.1%) and T25 (91.2%). Five of the other seven strains exhibit a homologous C-terminus (300 bp) on both ospA and ospB genes (88.7–97.3%). The other two strains seem to be derived from the five strains by ospA or ospB alterations. In a phylogenetic analysis based on ospA, these strains could be classified into B. garinii, but formed independent branches and separated from the typical B. garinii isolates from Europe and Russia.     

痛风性关节炎急性期、缓解期超声特征及与血清IL-22、IL-37水平的相关性研究

摘要 目的：探讨痛风性关节炎（GA）急性期、缓解期超声特征及与血清白细胞介素（IL）-22、IL-37水平的相关性。方法：选取从2019年7月至2021年3月期间，在我院诊断为GA的患者64例作为痛风组，及同期在我院体检的健康志愿者32例作为正常对照组。经过超声检查、血清样品实验后，观察受试者的超声特征，比较受试者血清IL-22、IL-37的水平，采用Spearman检验分析GA患者血清IL-22、 IL-37水平与超声特征的相关性。比较超声特征、IL-22和IL-37水平单一或联合应用对GA急性期、缓解期的诊断价值。结果：痛风组急性期血清IL-22水平显著高于缓解期及正常对照组(P＜0.05)；痛风组急性期及缓解期血清IL-37水平均显著高于正常对照组，且缓解期高于急性期(P＜0.05)。64例GA患者中有29例存在痛风石；60例在急性期存在关节积液，至缓解期有22例吸收至正常积液量；有52例在急性期关节滑膜增生，至缓解期有14例得以缓解;有29例存在"双轨征"，仅1例在缓解期消失;有14例发生骨侵蚀，在缓解期均未见明显改善；缓解期积液厚度、滑膜厚度均明显小于急性期(P＜0.05)。无论急性期还是缓解期，GA患者血清IL-22水平与关节积液均呈正相关(P＜0.05)。超声检查联合血清IL-22、IL-37水平检测用于诊断无论在急性期还是缓解期，其敏感性及特异性均较高。结论：IL-22水平不论在急性期还是缓解期，与超声下关节积液均呈正相关。血清IL-22、IL-37检测与超声检查联合可提高急性期及缓解期GA的诊断效能。     

Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity

Recent progress in the understanding of psoriasis has shown that the regulation of local and systemic cytokines plays an important role in its pathogenesis. The most often used psoriasis score is the psoriasis area and severity index (PASI). A simple laboratory test from a blood sample would be an attractive, patient-independent, and observer-independent marker of disease severity. To this end, we evaluated the association of serum levels of some proinflammatory cytokines in vivo and their correlation with severity of psoriasis. The serum levels of cytokines levels were determined with the use of the ELISA method. All mean values except IL-17 levels of patients were significantly higher than those of controls. There was a significant correlation between serum levels of IFN-gamma, IL-12, IL-17, and IL-18, and severity of the disease. Psoriasis can be described as a T-cell-mediated disease, with a complex role for a variety of cytokines, which has led to the development of new immunomodulatory therapies. In this study, serum TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, and IL-18 levels were significantly higher in active psoriatic patients than in controls. Furthermore, high levels of IFN-gamma, IL-12, and IL-18 correlated with the clinical severity and activity of psoriasis, and those measurements of serum levels of these cytokines may be objective parameters for the disease severity.