Graves' disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ

The role of genetic factors in the pathogenesis of Graves' disease (GD) is not clear. The purpose of this study was to investigate the association between single nucleotide polymorphisms in pro-inflammatory cytokine genes and GD in Iranian patients. A case-control hospital-based study was carried out on 107 GD patients and 140 healthy controls. Cytokine typing was performed by polymerase chain reaction with sequence-specific primers (PCR-SSP) assay. The allele and genotype frequencies of the following cytokine genes were determined: TNF-α (-308A/G, -238A/G), IL-2 (-330T/G, +166G/T), IL-6 (-174C/G, A/G nt565), IL-12 (-1188A/C), and IFN-γ (UTR 5644A/T). The following alleles and genotypes were significantly overrepresented in patients: TNF-α -308A allele (P < 0.01) and AA genotype (P < 0.05), IL-2 -330G allele (P < 0.01) and GG genotype (P < 0.01), IL-6 -174C allele (P < 0.01) and CC genotype (P < 0.01), IL-12 -1188C allele (P < 0.01) and CC genotype (P < 0.01), IFN-γ UTR5644T allele (P < 0.01) and TT genotype (P < 0.01). In conclusion, this is the first study to show a significant association between GD and IL-2 -330G, IL-12 -1188C, and IFN-γ UTR 5644T alleles. Our results support the hypothesis that polymorphism in pro-inflammatory cytokines might be involved in predisposition to GD.     

IL-10, TGF-ß, IL-2, IL-12, and IFN-γ Cytokine Gene Polymorphisms in Asthma

Asthma is a complex respiratory disease, characterized by airway inflammation and reversible airway obstruction. Both genetic and environmental factors are important in the development and expression of the disease. In order to analyze the genetic profile of Th1 and Th2 cytokines in Iranian asthmatic patients, this study was performed. The allele and genotype frequencies of a number of polymorphic genes coding for IL-10, TGF-ß, IL-2, IL-12, and IFN-γ were investigated in 60 patients with asthma in comparison with 140 controls. The most frequent genotypes in our patients were IL-10 GA at position-1082 (p = 0.001), IL-10 CT at position ?819 (p = 0.001), IL-10 CA at position ?592 (p = 0.0001), IL-12 CA at position ?1188 (p = 0.003), TGF-ß CG at codon 25 (p = 0.002), IL-2 GT at position -330 (p = 0.004). In contrast, the frequencies of the genotypes IL-10 AA at position ?1082 (p = 0.0001) and GG at position ?1082 (p = 0.01), IL-10 CC at position ?819 (p = 0.001) and TT at position -819 (p = 0.01), TGF-ß TT at codon 10 (p = 0.001), TGF-ß GG at codon 25 (p = 0.005), IL-12 AA at position ?1188 (p = 0.004), IL-2 TT at position ?330 (p = 0.01) were significantly lower in the patient group. The most frequent haplotypes in the patients were IL-10 GCC (p = 0.008) and ATA (p = 0.0001) at position ?1082, ?819, ?592, and TGF-ß CC (p = 0.036) at codon 10 and codon 25. In contrast, the frequencies of the IL-10 ACC (p = 0.001), TGF-ß TG (p = 0.024), and IL-2 TT (p = 0.001) and GT (p= 0.0001) in the patients were significantly lower than controls. Considering the high frequency of presence of IL-10 ATA haplotype and the IL-2 GT genotype, it seems that the production of IL-10 and IL-2 in the asthmatic patients could be lower than normal subjects.     

IL-1β, IL-6, IL-8, IL-10, IFN-γ, TNF-α and its relationship with lipid parameters in patients with major depression

There is some evidence that an immune response with an increased production of proinflammatory cytokines frequently accompanies major depression. The aim of this study was to determine the serum levels of interleukines (IL-1??, IL-6, IL-8, IL-10), tumor necrosis factor-alpha (TNF-??), interferon-gamma (IFN-??) and immonuglobulines (IgG, IgA and IgM) levels and to examine the relationships between all above parameters and lipid parameters. The study group included 30 patients and 30 healthy volunteers. Although total cholesterol, HDL-cholesterol, and IgM levels were increased significantly (p?<?0.05) in patients and compared to those of the controls, no statistically significant differences (p?>?0.05) were observed with other parameters. IFN-?? were positively correlated with total cholesterol (r?=?0.425; P?=?0.019) and LDL-cholesterol (r?=?0.391; P?=?0.032) levels in patients. Other cytokines and immunoglobulins did not show any correlation with lipid parameters. It was concluded that although no differences was observed in cytokines and immunoglobulin levels in the present study, the dysregulation of the lipids and immune system including the cytokine network is associated with the etiology and pathophysiology of major depressive disorders.     

Associations between polymorphisms in IL-12A, IL-12B, IL-12Rβ1, IL-27 gene and serum levels of IL-12p40, IL-27p28 with esophageal cancer

Purpose

The aim of this study was to investigate whether IL-12A, IL-12B, IL-12Rβ1, and IL-27 gene polymorphisms and serum levels of IL-12, IL-27 are associated with esophageal cancer.

Methods

We genotyped IL-12A gene rs568408, IL-12B gene rs3212227, IL-12Rβ1 gene 378 C/G, IL-27 gene rs153109, rs17855750, and rs181206 polymorphisms in a case–control study of 426 esophageal cancer patients and 432 health controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay.

Results

Both serum IL-12p40 and IL-27p28 levels were significantly higher in controls than those in patients (P?<?0.01). Rs568408 AG/AA, rs3212227 CC/AC, and IL-12Rβ1 378 GG/GC genotypes were associated with significantly increased risk of esophageal cancer (rs568408: χ²?=?5.704, P?=?0.017; rs3212227: χ²?=?7.689, P?=?0.006; IL-12Rβ1 378C/G: χ²?=?5.206, P?=?0.023). Moreover, rs3212227 CC/AC and 378 GG/GC genotypes were observed significantly associated with decreased serum IL-12p40 level in patients compare to other genotypes (rs3212227: t?=?2.129, P?=?0.034; IL-12Rβ1 378 C/G: t?=?2.178, P?=?0.030). Furthermore, frequency of rs3212227 CC/AC genotypes was significantly higher in patients with poor differentiation than those with AA genotype (χ²?=?4.314, P?=?0.035).

Conclusion

Our data suggest that the impaired production of IL-12p40 and IL-27p28 behaves as risk factors for esophageal cancer occurrence. IL-12B gene rs3212227 CC/AC and IL-12Rβ1 gene 378 GG/GC genotypes, which associated with decreased IL-12p40 level, may contribute to esophageal cancer susceptibility.     

冠心病患者血浆IL-10,IL-17,IL-18和C反应蛋白的水平检测

目的:探讨血浆白细胞介素(IL)-10,IL-17,IL-18和C反应蛋白(CRP)在冠心病发病过程中的作用及其临床意义。方法:采用酶联免疫双抗体夹心法(ELISA)对160例冠心病患者(急性心肌梗死50例,不稳定型心绞痛68例,稳定型心绞痛42例)和40例正常人血浆中IL-10,IL-17,IL-18和CRP的水平进行检测。结果:冠心病患者血浆IL-10,IL-17,IL-18和CRP的水平均显著高于正常对照组(P<0.05)。结论:IL-10作为冠心病的保护因子,不足以阻止其发生、发展,IL-17,IL-18和CRP的水平与冠心病的发生与发展相关,其水平的检测对冠心病诊断及病情判断有重要意义。     

Clinical significance of IL-18, IL-15, IL-12 and TNF-α measurement in rheumatoid arthritis

The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-α) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-α were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-α levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-α were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-α (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-α and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-α levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.     

IL-1,IL-1受体拮抗与肾脏病

白细胞介素1(interlcukinc,1 IL-1)是一种多肽生长因子,在炎症及免疫调节等方面起重要作用,具有广泛的生物学活性.近年研究表明,肾脏病发生发展的病理生理过程,常有IL-l的介导、参与,肾小球的系膜细胞也能自分泌IL-1.应用lL-1受体拮抗剂治疗某些肾炎的动物模型可获一定疗效。本文概述IL-1的生物学活性、lL-1受体拮抗剂在肾脏病中的应用.     

肝纤维化与TNF-alpha, IL-6及IL-10

肝纤维化(LF)是各种原因引起的慢性肝损伤所共有的细胞病理过程,其特征为大量细胞外基质(ECM)在Disse间隙沉积。近来,由于细胞生物学及细胞因子信号传导研究领域中取得的重大进展,越来越多的证据表明,肝纤维化是可以逆转的。各种细胞因子通过复杂的调节机制在肝纤维化的进展中起重要作用,从而使对细胞因子和肝纤维化的研究成为热点之一。     

IL-1β,IL-2,IL-10在糖耐量减低并血管性痴呆患者发病中的作用

目的探讨白细胞介素(IL)在糖耐量减低(IGT)并发血管性痴呆患者发病中的作用。方法选择血管性痴呆患者100例分成血管性痴呆组和血管痴呆合并IGT组各50例;然后再随机选取健康人50例对照组。检测空腹血糖(FPG)、餐后2 h血糖(2 h PG)和IL-1β、IL-2、血清IL-10水平。结果血管痴呆合并IGT组跟对照组、血管性痴呆组相比,2 h PG明显升高(P0.01);血管性痴呆组、血管痴呆合并IGT组跟对照组相比,血IL-1β水平明显升高(P0.05),血IL-2水平明显升高(P0.05),血清IL-10水平明显升高(P0.05),且血管痴呆合并IGT组明显高于血管性痴呆组的(P0.05)。结论在血管性痴呆合并IGT患者体内,IL水平升高明显,说明血管性痴呆合并IGT患者体内炎症反应增强。     

肝纤维化与TNF-α, IL-6及IL-10

肝纤维化(LF)是各种原因引起的慢性肝损伤所共有的细胞病理过程,其特征为大量细胞外基质(ECM)在Disse间隙沉积[1-5].近来,由于细胞生物学及细胞因子信号传导研究领域中取得的重大进展,越来越多的证据表明,肝纤维化是可以逆转的[6-10].各种细胞因子通过复杂的调节机制在肝纤维化的进展中起重要作用[11-15],从而使对细胞因子和肝纤维化的研究成为热点之一.     

Expansion of human NK-22 cells with IL-7, IL-2, and IL-1β reveals intrinsic functional plasticity

Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the sur-vival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1β or IL-2 to IL-7 and was even stronger in the presence of IL-1β plus IL-2. In contrast to IL-7, continuous culture in IL-1β and IL-2 modified NK-22 cytokine profiles. IL-1β promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-γ and leukemia inhibitory factor. Functional deviation toward IFN-γ production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell–mediated mucosal immunity.     

病毒性肝炎患者血清IL-6,IL-8水平及临床意义

了解病毒性肝炎患者血清IL－6、IL－8水平及临床意义。应用放射免疫法检测124例病毒性肝炎患者血清IL－6、IL－8水平并动态观察，其中35例慢性肝炎进行肝活检，并按肝组织病理进行分级和分期。①急性肝炎、慢性肝炎中重度、慢性重型肝炎IL－6和IL－8水平依次升高，明显高于正常对照（P＜0．01）；②IL－6、IL－8水平与肝 组织炎症坏死程度和肝纤维化程度呈正相关（P＜0．01，P＜0．01）；③IL－6、IL－8水平随急性肝炎恢复和慢性肝炎稳定而降低（P＜0．01，P＜0．05）。IL－6、IL－8水平可作为反映肝细胞坏死程度和纤维化轻重的指标。     

脑出血患者外周血IL-17,IL-23的表达及意义

<正>目前脑出血治疗缺乏特异、有效手段,其原因主要是脑出血后血肿周围组织损伤机制尚未完全阐明。大量研究证实炎症反应参与脑出血后的病理过程。本研究拟探讨脑出血患者外周血白介素(IL)-17、IL-23的表达及意义。1材料与方法1.1主要试剂人IL-17 ELISA检测试剂盒、IL-23 ELISA检测试剂盒,美国R&D公司。1.2实验分组实验组:脑出血患者48例,来自吉林大学白     

HIV感染者血清TNF-α,IL-2各IL-6的变化

人类免疫缺陷病毒(HIV)感染所引起的免疫病理机制中细胞因子的作用及细胞因子网络失衡是其中的一个重要方面,国内尚无报道。为研究TNF-a、IL-2和11-6分泌水平在我国HIV感染者的异常,进一步探讨有针对性的艾滋病(AIDS)治疗方案,对HIV感染者32例进行了血清TNF-a.IL-2和IL-6测定,报告如下。 1 材料和方法 1.1 材料 HIV感染组32例,男,年龄18～42(平均28)岁.为强制戒毒劳教人员,吸毒方式均为静脉吸毒,吸毒史3a-9a。HIV抗体检测采用酶联免疫吸附试验(ELISA)初筛,阳性者经蛋白印迹法(WB)确证.正常对照组40例,为健康体检者,男22例,女18例,年龄18岁～50岁,平均32岁。以上检测对象     

Serum Levels of Interleukins (IL)-4, IL-5, IL-13, and Interferon-γ in Acute Asthma

T-cell activation and alteration of cytokine levels are involved in the pathogenesis of bronchial asthma. However, the profile of circulating T-lymphocyte subsets and related cytokines during acute asthmatic attacks is still unclear. We hypothesized that serum levels of interleukin (IL)-4, IL-5, and IL-13 would be increased, whereas IFN-γ would be decreased in acute asthma. The subjects enrolled in this study included 58 acute asthmatics, 22 asymptomatic asthmatics, and 10 healthy controls. Serum levels of IL-4, IL-5, IL-13, and IFN-γ were measured using a sandwich enzyme-linked immunosorbent assay. We correlated serum levels of IL-4, IL-5, IL-13, and IFN-γ with initial forced expiratory volume in 1 sec (FEV₁). Compared with control subjects, acute asthmatics had significantly increased levels of circulating IL-4 (p < 0.001), IL-5 (p < 0.001), and IL-13 (p < 0.001), although the differences were of borderline significance in serum IFN-γ (p = 0.069). There were also significant differences in the circulating levels of IL-4, IL-5, and IL-13 between acute asthmatics and asymptomatic asthmatics. There was no significant association between initial FEV₁ and serum levels of IL-4 or IL-13, however, among acute asthmatics, a lower initial FEV₁ was associated with higher IL-5 and/or lower IFN-γ levels. Our results suggest that serum levels of IL-4, IL-5, and IL-13 may be elevated in acute asthma, and that higher levels of IL-5 and/or lower levels of IFN-γ are associated with severe airway obstruction.     

Bacterial Translocation Is Linked to Increased Intestinal IFN-γ, IL-4, IL-17, and mucin-2 in Cholestatic Rats

Background and rationale for the study. Bacterial translocation is an important triggering factor of infection and mortality in cirrhosis. In a rat model using bile duct ligation (BDL), bacterial translocation appears within 24 h after ligation. The dynamic between TH1/TH2/TH17 cytokines and the integrity of the colonic mucosa in the context of cirrhosis is little known. This study aims to determine the link between bacterial translocation and intestinal inflammation in a cholestasis model. Additionally, alterations of the colonic mucus layer and the bacterial load were also addressed.Results. Bacterial translocation detected by microbiological cultures and MALDI-TOF showed that Escherichia coli predominates in mesenteric lymph nodes of BDL rats. Intestinal bacterial load analyzed by qPCR indicates a dramatic Escherichia/Shigella overgrowth at 8 and 30 days post-BDL. IFN-γ, IL-4, and IL-17 evaluated by Western blotting were increased at 8 and 30 days in the small intestine. In the colon, in contrast, only IFN-γ was significantly increased. The colonic mucus layer and mucin-2 expression determined by Alcian blue staining and immunohistochemistry surprisingly showed an increase in the mucus layer thickness related to increased mucin-2 expression during the entire process of liver damage. Hepatic enzymes, as well as collagen I, collagen III, TNF-α, and IL-6 liver gene expression were increased.In conclusion, bacterial overgrowth associated with bacterial translocation is linked to the over-expression of IFN-γ, IL-4, IL-17 and mucin-2. These molecules might facilitate the intestinal permeability through exacerbating the inflammatory process and disturbing tight junctions, leading to the perpetuation of the liver damage.     

慢性乙型肝炎患者T细胞亚群,mIL-2R,sIL-2R,IL-6,IL-8,TNF-α变化及意义

目的探讨病毒性肝炎(乙肝)患者T细胞亚群,mIL-2R,sIL-2R,IL-6,IL-8,TNF-α与乙肝发病机制的关系.方法采用APAAP技术和ELISA法检测92例慢性乙型肝炎患者T细胞亚群,mIL-2R和血清sIL-2R,IL-6,IL-8,TNF-α水平.结果慢性乙型肝炎患者CD4+细胞数较正常低(P＜0.05),对照组和实验组(慢性乙肝轻度、慢性乙肝中重度、肝炎后肝硬变、重症肝炎)的CD4+数值分别为:(45.6±3.6)%,(39.7±10.2)%,(40.6±11.0)%,(39.0±6.5)%,(31.2±8.9)%.CD9+细胞数显著上升(P＜0.05或P＜0.01),对照组和实验各组依次为:(28.7±3.2)%,(35.4±9.5)%,(38.7±7.6)%,(42.2±9.4)%,以致CD4+/CD8+比值下降;mIL-2R显著低于正常对照组(P＜0.05),在PHA激活后与正常接近,但均较PHA激活前显著增高(P＜0.01);PHA激活前的mIL-2R对照组与实验组分别为:(15.69±4.32)%,(3.98±5.36)%,(9.37±5.48)%,(9.77±5.76)%,(9.58±5.45)%.PHA激活后mIL-2R对照组与实验组分别为:(69.82±5.36)%,(67.98±3.69)%,(69.11±2.19)%,(63.93±1.32)%,(66.32±5.26)%.慢性乙肝患者血清中sIL-2R,IL-6,IL-8,TNF-α分别为:(798.9±69.0)ng/L,(2806.2±211.7)ng/L,(480.6±32.4)ng/L.正常对照组＜100ng/L,且在慢性肝炎、肝硬变活动期与稳定期之间、重型肝炎的肝坏死与恢复期之间,血清IL-6,IL-8,TNF-α三项指标的差异有显著性,均P＜0.001.结论乙肝患者存在免疫调节紊乱,而免疫异常至少有部分原因是细胞因子的作用.