Occupational exposure to trichloroethylene and serum concentrations of IL‐6, IL‐10, and TNF‐alpha

To evaluate the immunotoxicity of trichloroethylene (TCE), we conducted a cross‐sectional molecular epidemiology study in China of workers exposed to TCE. We measured serum levels of IL‐6, IL‐10, and TNF‐α, which play a critical role in regulating various components of the immune system, in 71 exposed workers and 78 unexposed control workers. Repeated personal exposure measurements were taken in workers before blood collection using 3 M organic vapor monitoring badges. Compared to unexposed workers, the serum concentration of IL‐10 in workers exposed to TCE was decreased by 70% (P = 0.001) after adjusting for potential confounders. Further, the magnitude of decline in IL‐10 was >60% and statistically significant in workers exposed to <12 ppm as well as in workers with exposures ≥ 12 ppm of TCE, compared to unexposed workers. No significant differences in levels of IL‐6 or TNF‐α were observed among workers exposed to TCE compared to unexposed controls. Given that IL‐10 plays an important role in immunologic processes, including mediating the Th1/Th2 balance, our findings provide additional evidence that TCE is immunotoxic in humans. Environ. Mol. Mutagen. 54:450–454, 2013. © 2013 Wiley Periodicals, Inc.     

Association of Interleukin‐1 beta and tumor necrosis factor‐alpha genetic polymorphisms with gastric cancer in India

Interleukin 1 beta (IL‐1β) and Tumor necrosis factor alpha (TNF‐α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL‐1β and TNF‐α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL‐1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30‐2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67‐3.83) and TNF‐α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54‐3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 “effective” risk alleles conferred a risk of almost 10‐fold in comparison to individuals carrying less than 3 “effective” risk alleles. Our survival analysis also indicated a significant association between IL‐1β rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL‐1β rs1143627:CC and rs16944:TT genotypes. Further, meta‐analysis revealed significant association of IL‐1β rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18‐14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48‐20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653–667, 2018. © 2018 Wiley Periodicals, Inc.     

Levels of Interleukin‐(IL)‐12p40 are Markedly Increased in Brucellosis Among Patients with Specific IL‐12B Genotypes

Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T‐helper 1 (Th1) cytokines such as interleukin‐12 (IL‐12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL‐12p40 cytokine (IL‐12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL‐12p40. We genotyped IL‐12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case‐control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL‐12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429–0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218–0.900 for the CC genotype). Comparison of IL‐12B genotypes and serum levels of the IL‐12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL‐12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL‐12p40 and could possibly contribute to an inherited predisposition to brucellosis.     

Polymorphism in the Interleukin‐7 Receptor‐alpha and Outcome after Allogeneic Hematopoietic Cell Transplantation with Matched Unrelated Donor

Interleukin‐7 (IL‐7) is essential for T cell development in the thymus and maintenance of peripheral T cells. The α‐chain of the IL‐7R is polymorphic with the existence of SNPs that give rise to non‐synonymous amino acid substitutions. We previously found an association between donor genotypes and increased treatment‐related mortality (TRM) (rs1494555G) and acute graft versus host disease (aGvHD) (rs1494555G and rs1494558T) after hematopoietic cell transplantation (HCT). Some studies have confirmed an association between rs6897932C and multiple sclerosis. In this study, we evaluated the prognostic significance of IL‐7Rα SNP genotypes in 590‐recipient/donor pairs that received HLA‐matched unrelated donor HCT for haematological malignancies. Consistent with the primary studies, the rs1494555GG and rs1494558TT genotypes of the donor were associated with aGvHD and chronic GvHD in the univariate analysis. The Tallele of rs6897932 was suggestive of an association with increased frequency of relapse by univariate analysis (P = 0.017) and multivariate analysis (P = 0.015). In conclusion, this study provides further evidence of a role of the IL‐7 pathway and IL‐7Rα SNPs in HCT.     

支气管哮喘患者血清中VEGF、 EGF等相关生长因子表达及与临床表型、肺功能以及病情程度相关性研究

目的 研究支气管哮喘患者血清中表皮生长因子(EGF)、碱性成纤维细胞生长因子(bFGF)、血小板衍生生长因子(PDGF)以及血管内皮生长因子(VEGF)的表达特征及其与BA发生、BA患者肺功能、病情程度以及临床表型间的相关性.方法 选取本院2016年1月至2017年1月间收治的72例支气管哮喘患者纳入研究组,以同期在本院接受健康体检的72例健康受检者作为对照组,对比两组各项生长因子的表达水平;分别根据临床表型、肺功能以及病情程度将研究组患者划分为相应亚组,对比各亚组间各项生长因子的表达水平,以明确支气管哮喘患者血清中各项相关生长因子的表达特征;分析各项生长因子表达水平与各亚组间的相关性.结果 研究组患者VEGF、EGF、bFGF、PDGF-AA、PDGF-BB表达水平与对照组受检者间差异均具有统计学意义,P＜0.05;研究组中嗜酸粒细胞表型患者的VEGF、EGF、bFGF、PDGF-AA、PDGF-BB表达水平与中性粒细胞表达患者差异均具有统计学意义,P＜0.05;研究组中FEV1＜50％患者的VEGF、EGF、bFGF、PDGF-AA、PDGF-BB表达水平与FEV1≥50％患者差异均具有统计学意义,P＜0.05;轻度亚组、中度亚组与重度亚组间VEGF、EGF、bFGF、PDGF-AA、PDGF-BB表达水平差异均具有统计学意义,P＜O.05.VEGF、EGF、PDGF-AA表达水平与BA疾病发生间具有高度相关性,P＜0.05;VEGF、EGF、bFGF、PDGF-AA、PDGF-BB与BA临床不同表型、肺功能及病情程度间均具有相关性,P＜0.05.结论 支气管哮喘患者血清中EGF、b FGF、PDGF、VEGF表达水平与健康者比较具有明显特征,并且各项生长因子的表达水平与患者的临床表型、肺功能以及病情程度具有明确的相关性.     

Interleukin‐33 Triggers B1 Cell Expansion and Its Release of Monocyte/Macrophage Chemoattractants and Growth Factors

B1 B lymphocytes are natural IgM‐producing cells primarily found in peritoneum and mucosal sites. They perform vital functions during the early defence against viral and bacterial infections. Murine B1 cells express IL‐33 receptor complex on activation. IL‐33 is a new addition to the IL‐1 family with a strong role in Th2 immunity. B1 cells have been recognized to exacerbate contact sensitivity by producing IgM and IL‐5 in response to interleukin‐33. However, the exact response of IL‐33/ST2 signalling in B1 cells is not completely understood. In this study, we report that murine B1 cells respond directly to IL‐33 in a ST2‐dependent manner. This interaction instigates B1b cell proliferation in a time‐dependent manner in vivo. Furthermore, it also mediates monocyte/macrophage and granulocyte recruitment via B1 cell release of chemokines (MCP‐1 and MIP‐1 alpha). It was noted that upon stimulation, B1b cells additionally release an angiogenic inducer vascular endothelial growth factor and granulocyte–monocyte colony‐stimulating factor (GM‐CSF). Our findings suggest that these IL‐33‐mediated B1 cells might be able to play a vital role in the recruitment and growth of monocytes and granulocytes.     

Genetic polymorphisms of tumour necrosis factor alpha (TNF‐α) promoter gene and response to TNF‐α inhibitors in Spanish patients with inflammatory bowel disease

Tumour necrosis factor alpha (TNF‐α) has an important role in inflammatory response. Alterations in the regulation of TNF‐α have been implicated in a variety of inflammatory disorders, including Inflammatory bowel disease (IBD). Indeed, a common treatment for IBD is the use of TNF‐α inhibitors. Polymorphisms in the TNF‐α promoter region are known to affect the level of gene expression. Our aim was to investigate the influence of these single nucleotide polymorphisms (SNPs) in TNF‐α promoter gene play in the risk of IBD in a Spanish population and their individual response to anti‐TNF‐α treatment. DNA samples from patients with IBD and controls were screened for TNF‐α ?238G/A (rs361525) and ?308G/A (rs1800629) SNPs by PCR‐SSOP using a microbeads luminex assay and compared with response to TNF‐α inhibitors. There were not statistical differences in ?238G/A and ?308G/A allele and genotype frequencies between patients. However, we found an increased frequency of ?308A allele and ?308GA genotype in these nonresponders patients to TNF‐α inhibitors with respect to responders patients (Pc < 0.05). This ?308GA genotype has been classified as high producer of this cytokine. This fact could actually be interesting to explain the different response of patients with IBD with respect to TNF‐α inhibitors. TNF‐α promoter gene polymorphism does not seem to play a role in IBD susceptibility, but particular TNF‐α genotypes may be involved in the different responses to TNF‐α inhibitor treatment in Spanish patients with IBD.     

抑郁发作患者的述情障碍及相关因素

本文探讨抑郁发作患者述情障碍与自测健康状况的关系,并分析住院抑郁发作患者述情障碍的影响因素. 1 对象及方法 1.1 对象 抑郁发作组:2006年12月～2007年12月在本院住院的患者105例.入组标准:①符合美国精神疾病诊断与分类手册第四版(DSM-IV)中关于抑郁发作的诊断标准;②无严重躯体疾病;③小学以上文化.回收有效问卷98份.其中男61例,女37例,年龄(28±10)岁;抑郁自评量表总分(42.2±8.2)分.     

痴呆患者经济负担及相关因素研究

目的:探讨痴呆患者的经济负担及其相关因素。方法:自行设计痴呆患者经济负担调查表,对46例患者家属进行调查。结果:①痴呆患者与痴呆相关的总花费平均1296±736元/月,其中非医疗费用600±502元/月(47.07%),医疗费用703±533元/月(52.93%)。②经济负担大小与简明精神症状检查表(MMSE)得分呈负相关。③不同MMSE 得分者的总费用、非医疗费用、每天需照顾的时间有显著差异,而医疗费用差异不明显。④伴有痴呆相关的行为及精神症状的患者总费用、医疗费用、非医疗费用、照顾时间均与不伴这些症状者有显著差异。结论:痴呆患者的经济负担大小与认知损害的程度及有无伴发精神行为障碍有关。     

Interleukin‐21 Induces Proliferation and Proinflammatory Cytokine Profile of Fibroblast‐like Synoviocytes of Patients with Rheumatoid Arthritis

Fibroblast‐like synoviocytes (FLS) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA) through aggressive proliferation and invasion, and certain proinflammatory cytokines may affect synoviocyte proliferation. To evaluate whether interleukin‐21 (IL‐21) could promote proliferation and proinflammatory cytokine production by RA‐FLS, immunohistochemistry and immunoblotting were performed to observe the expression of IL‐21 receptor (IL‐21R) in synovial tissues and FLS from RA and osteoarthritis (OA) patients. The MTS assay was used to analyse RA‐FLS proliferation. The concentrations of IL‐6 and tumour necrosis factor‐α (TNF‐α) in culture supernatants were determined by enzyme‐linked immunosorbent assay (ELISA). The signalling pathways triggered by IL‐21 were characterized by immunoblotting. IL‐21R was upregulated in the synovial tissues and FLS of RA patients as compared with OA patients. IL‐21 stimulated RA‐FLS proliferation and promoted the production of TNF‐α and IL‐6 and blockade of IL‐21/IL‐21R pathway with IL‐21R.Fc attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. Moreover, IL‐21 induced activation of the ERK1/2, PI3K/AKT and STAT3 pathways, and blockade of these pathways attenuated IL‐21‐induced proliferation and secretion of TNF‐α and IL‐6. These results suggest that IL‐21 could promote RA‐FLS proliferation and production of proinflammatory cytokines. Therefore, therapeutic strategies targeting IL‐21 might be effective for the treatment of RA.     

支气管哮喘患儿内皮素-1及相关炎性细胞因子测定

目的:探讨内皮素及相关炎性细胞因子在小儿哮喘发病机制中的作用。方法:分别用放射免疫分析及酶免法测定了42例哮喘患儿治疗前后内皮素-1、白细胞介素-5、白细胞介素-6及白细胞介素-8水平。结果:发作期组内皮素水平高于缓解组及对照组差异非常显著(P值均<0 01),缓解组较发作组水平下降显著但仍显著高于对照组(P<0 05)。3种细胞因子水平则发作期组均显著高于缓解组及对照组,统计差异极显著(P值均<0 01),缓解组前2种细胞因子仍显著高于对照组(P值均<0 05);而后一种细胞因子已下降至近对照组水平(P>0 05)。ET与IL-5呈显著正相关(发作期r=0 560,P<0 01;缓解期r=0 435,P<0 01)。结论:内皮素与细胞因子以不同方式参与了小儿哮喘的发病机制,其测定对于评价炎症程度及疗效、指导临床治疗有重要意义。     

高脂血症者血清 TG 与 leptin 及相关因子含量的相关性

目的:探讨高三酰甘油血症者血清中三酰甘油(TG)、瘦素(leptin)、白细胞介素-1(IL-1)、神经肽Y(NPY)、脂联素(ADP)的含量变化及其相关性.方法:选54例TG含量高者作为实验组,55例TG正常者为对照组.应用放射免疫分析测定两组血清中的TG、瘦素、NPY、IL-1、脂联素含量.结果:HTG组中TG、瘦素、IL-1、NPY含量[(3.46±1.14)mmol/L,(10.56±3.79)μg/L,(0.40±0.18)μg/L,(115.89±24.56)μg/L]均高于正常组的含量[(1.26±0.30)mmol/L,(5.66±2.01)μg/L,(0.22±0.09)μg/L,(95.21±6.85)μg/L,P均＜0.01];HTG组中脂联素含量(8.98±3.51μg/L)低于正常组的含量[(13.21±9.46)μg/L,P＜0.01].其中TG与瘦素含量呈正相关(r=0.576;P＜0.05);瘦素分别与IL-1及与NPY含量亦呈正相关(r=0.582;r=0.479,P均＜0.05).结论:(1)HTG者TG含量的增高与瘦素、NPY、IL-1、脂联素含量变化相关;(2)TG与瘦素、NPY、IL-1之间存在着相互的调节作用;(3)神经-内分泌-免疫系统影响脂代谢造成的HTG.     

支气管哮喘心理社会因素与细胞因子及内皮素变化的关系

目的:探讨支气管哮喘患者的个性、生活事件及心理健康状况与相关细胞因子白介素(IL):IL-2、IL-4、IL-8、IL-10、γ-干扰素(IFN-γ)和内皮素(ET-1)在发病过程中变化的相关性.方法:对60例支气管哮喘患者和30例对照者,进行了艾森克人格(EPQ)、生活事件(LES)和心理健康状况(SCL-90)评定及IL-2、IL-4、IL-8、IL-10、IFN-γ与ET-1检测.结果:病人组EPQ测试:E得分明显低于对照组(P＜0.05),N得分高于对照组(P＜0.05);P、L得分虽有差异但无统计学意义;生活事件总分,病人组明显高于对照组(P＜0.01);SCL-90测评:病人组除偏执、精神病因子分与对照组差异无统计学意义外(P＞0.05),其余因子分和总分研究组高于对照组,差异有显著性(P＜0.05、0.01).血清IL-2、IL-10和IFN-γ研究组低于对照组(P＜0.01),IL-4、IL-8和ET-1研究组高于对照组(P＜0.05、0.01).相关性分析显示,在支气管哮喘发病过程中IL-2、IL-10和IFN-γ的变化与性格E呈正相关(r=0.24、0.36、0.40,P＜0.05、0.01),与性格N呈负相关(r=-0.33、-0.35、-0.30,P＜0.05、0.01);而IL-4、IL-8和ET-1与性格E呈负相关(r=-0.33、-0.42、-0.47,P＜0.05、0.01);与性格N呈正相关(r=0.61、0.38、0.47,P＜0.05、0.01);IL-4、IL-8和ET-1与SCL-90和LES得分呈正相关(r=0.54、0.37、0.49、0.34、0.38、0.32,P＜0.05、0.01);IL-2、IL-10和IFN-γ与SCL-90和LES得分呈负相关(r=-0.19、-0.32、-0.49、-0.44、-0.27、-0.51,P＜0.05、0.01).结论:支气管哮喘患者的个性具有神经质特征,心理健康水平较低,一年内的生活事件较多.在支气管哮喘发病中,血清IL-2、4、8、10、IFN-γ和ET-1有明显变化,而且与患者个性特征、生活事件和心理健康水平均有一定程度的显著相关性.     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.