骨桥蛋白及白细胞介素-18在系统性红斑狼疮患者血浆中的表达及意义

目的：探讨系统性红斑狼疮（SLE）患者血浆骨桥蛋白（OPN）、白细胞介素-18（IL-18）表达的临床意义。方法：采用酶联免疫吸附试验（ELISA）检测90例SLE患者及30例对照血浆OPN、IL-18的水平,以分析其与SLE的活动性及脏器损害的关系。结果：SLE患者血浆OPN、IL-18水平显著高于健康对照组（P〈0.001）;狼疮性肾炎（LN）患者血浆OPN、IL-18水平明显高于无脏器损害者（P均〈0.01）;SLE活动期亦高于非活动期（P均〈0.01）。相关分析表明,血浆OPN水平与IL-18呈正相关（r=0.331,P〈0.01）;血浆OPN及IL-18水平与SLE疾病活动指数（SLEDAI）呈正相关（r=0.573,P〈0.001;r=0.315,P均〈0.01）;与24h尿蛋白定量亦呈正相关（r=0.532,r=0.403,P均〈0.01）;而与补体C3呈负相关（r=-0.472,P〈0.01;r=-0.398,P均〈0.01）。结论：OPN、IL-18可参与SLE的发病,与SLE的肾脏损害、活动程度具有相关性,联合检测血浆OPN、IL-18可以作为诊断SLE活动性及LN诊断的有效的指标之一。     

白细胞介素-23和白细胞介素-15在过敏性紫癜患者血清中的表达及临床意义

目的:探讨白细胞介素-23(IL-23)、白细胞介素-15(IL-15)在过敏性紫癜(HSP)患者血清中的表达及临床意义.方法:选取2014年3月-2016年12月我院41例HSP患者(观察组),同期体检健康者37例设为对照组.观察组于入院后第二天清晨、对照组于体检当日取空腹静脉血检测血清IL-23和IL-15水平.41例HSP患者于治疗2周后,根据临床疗效分为有效组(n=29)与无效组(n=12),再取血清测定IL-23和IL-15水平进行比较.结果:观察组血清IL-23、IL-15水平高于对照组,差异有统计学意义(P＜0.05):治疗2周后,有效组患儿血清IL-23、IL-15水平显著低于无效组,差异有统计学意义(P＜0.05).结论:IL-23与IL-15可能参与了HSP发病过程,检测血清IL-23、IL-15水平有利于辅助临床有效评估HSP治疗效果.     

狼疮肾炎患者血清和尿白细胞介素-18水平检测及其临床意义

目的：检测狼疮肾炎(LN)患外周血清和尿液白细胞介素—18(IL—18)水平并探讨其临尿意义。方法：血清和尿液IL-18含量采用酶联免疫吸附方法(ELISA)。结果：LN组血清IL—18水平显高于正常对照组(P＜0、01)，活动期LN血清IL—18水平显高于缓解期患(P＜0．01)3LN组尿IL—18水平显高于正常对照组(P＜0．05)，活动期LN患尿IL—18水平显高于缓解期患(P＜0．05)。LN患血清IL—18水平与SLEDAI、抗dsDNA抗体成正相关关系，与补体C3呈负相关关系，而与血白蛋白、血肌酐无相关关系；活动期LN患尿IL—18水平与狼疮肾组织活动性指数(AI)、24h尿蛋白排泄量均呈正相关关系。结论：LN血清和尿IL—18水平显增高，IL—18可能在LN的病理生理过程中起重要作用。LN血清和尿IL—18水平均与狼疮病情活动密切相关，可作为判断狼疮疾病活动性的候选参考指标。     

白细胞介素-18与免疫性肾损伤

白细胞介素 1 8是一种Th1类细胞因子 ,它主要由活化的单核 巨噬细胞产生 ,与白细胞介素 1 β有相似的结构 ,而与白细胞介素 1 2有相似的生物学功能 ,特别是具有极强的诱生γ 干扰素和增强NK细胞的细胞毒能力。可能在感染、肿瘤和自身免疫性疾病等方面起重要作用。作为一种免疫调节因子 ,研究IL 1 8在肾小球疾病中的作用对进一步明确免疫性肾损伤的发病机制和寻找治疗该类疾病的新途径具有潜在的价值     

白细胞介素-18在大鼠脓毒症中的改变及其与内毒素血症的关系

白细胞介素 18(IL 18)最初名为干扰素 γ(IFN γ)诱导因子 ,是近年新发现的一种重要促炎细胞因子 ,在机体感染与免疫过程中具有一定作用[1] 。我们采用大鼠盲肠结扎穿孔术 (CLP)所致脓毒症模型 ,探讨了主要器官IL 18基因表达的改变及其意义。一、材料与方法1.动物模型 :雄性Wistar大鼠 ,体重2 2 0～ 3 0 0 g ,依照Chaudry等[2 ] 方法复制CLP致脓毒症模型。动物 72h死亡率为75 %。2 .动物分组及处理 :将 5 4只动物随机分为 3大组 :正常对照组 ( 6只 ) ,动物麻醉后活杀 ;CLP组 ( 3 6只 ) ,分别于CLP术后 2、6、12、2 4、48、72h活…     

白细胞介素-17和白细胞介素-6在肝内胆管细胞癌的表达及其临床意义

目的 探讨肝内胆管细胞癌(ICC)白细胞介素-17(IL-17)和白细胞介素-6(IL-6)表达的临床意义.方法 采用免疫组织化学Envision二步染色法检测69例ICC肿瘤组织和63例癌旁组织IL-17和IL-6的表达,分析两者的关系及其与临床病理特征和预后的关系.结果 肿瘤和癌旁组织中IL-17+细胞密度中位值分别为36.0/HP(每高倍视野)和8.0/HP;肿瘤组织IL-17低表达组和高表达组IL-6阳性表达率分别为46.9％和75.0％;IL-17和IL-6的表达呈正相关(r=0.256,P＜0.05);肿瘤组织IL-17低表达组术后生存时间较长(P＜0.01),Cox多因素分析提示肿瘤组织IL-17表达水平( HR=2.462,P＜0.05)是ICC患者术后的独立预后因素.结论 ICC肿瘤组织IL-17表达与IL-6表达呈正相关,与ICC患者术后生存呈负相关,可作为预测患者预后的指标.     

白细胞介素-6和白细胞介素-10在不同细菌性血流感染小鼠模型中的表达及意义

目的:探讨白细胞介素(IL)-6和IL-10在不同病原菌所致细菌性血流感染中的表达及其意义.方法:建立金黄色葡萄球菌、粪肠球菌、大肠杆菌和肺炎克雷伯菌ICR小鼠血流感染模型,以注射相应剂量磷酸盐缓冲液的小鼠作为对照组,采用Luminex液相悬浮芯片系统检测各实验组和PBS对照组感染后0.5、1、3、6、12、24和48h时IL-6和IL-10的含量.结果:细菌感染小鼠后0.5 h时,各实验组IL-6的含量与对照组相比均明显升高(P＜0.05).各实验组IL-10的水平与对照组相比,感染后0.5h均明显升高(P＜0.05).大肠杆菌组、肺炎克雷伯菌组IL-10的含量在感染后1h达最大值.金黄色葡萄球菌组感染后3h达到最大值,粪肠球菌组在感染后6h达到最大值,且大肠杆菌组和肺炎克雷伯菌组IL-6和IL-10含量升高的幅度明显高于金黄色葡萄球菌组和粪肠球菌组(P＜0.05).对照组小鼠血清中IL-6和IL-10的含量在此过程中无明显变化.结论:IL-6和IL-10的含量在4种细菌性血流感染模型早期均明显升高.大肠杆菌组、肺炎克雷伯菌组IL-6和IL-10的含量升高幅度明显高于金黄色葡萄球菌组和粪肠球菌组.联合运用IL-6和IL-10有可能用于区分革兰阳性或革兰阴性细菌感染.     

表达白细胞介素-18的结肠癌瘤苗抗肿瘤作用及其机制

目的 观察表达人白细胞介素(hIL)-18的结肠癌移植瘤新生血管生成及肿瘤生长.方法 0.1 ml单克隆化的人结肠癌sw480细胞、携有绿色荧光蛋白表达质粒的pEGFP-sw480细胞、携有hIL-18基因表达质粒的hIL-18.pEGFP-sw480细胞(1×108个/ml)分别注射裸鼠,每组5只.ELASA法检测裸鼠血清IL-18含量;记录成瘤时间及瘤体大小;免疫组织化学法检测移植瘤组织VEGF、MMP-9及微血管密度(CD34表达);TUNEL法检测移植瘤组织凋亡.结果 hIL-18-pEGFP-sw480组成瘤时间为(26.2±1.8)d,而pEGFP-sw480、sw480组分别为(14.8±2.8)d和(14.6±1.9)d.注射42 d后,hIL-18-pEGFP-sw48组裸鼠血中IL-18含量为(63.58±13.75)ng/L.hIL-18-pEGFP-sw480、pEGFP-sw480、sw480组肿瘤平均体积(mm3)分别为:336.39±28.50、1029.08±114.84、957.96±91.55.ML-18-pEGFP-sw480组肿瘤明显小于sw480组和pEGFP-sw480组(P<0.01).微血管密度(CD34)分别为(9.08±4.01)、(32.48±8.84)、(33.32±3.39),MMP-9灰度值分别为143.2±6.8、114.6±5.4、110.2±5.9;VEGF灰度值分别为140.8±9.2、108.5±8.7、107.3±4.9,hIL-18.pEGFP-sw480组血管生成及促血管生成因子表达明显减少;hIL-18-pEGFP-sw480组凋亡细胞阳性率(30.32±7.23)%明显高于pEGFP-sw480组(6.32±1.18)%和sw480组(5.80±2.28)%(P<0.01).结论 IL-18可明显减少裸鼠结肠癌sw480细胞移植瘤的血管生成,促进肿瘤细胞凋亡,抑制肿瘤生长.     

白细胞介素18在肿瘤治疗中的研究进展

IL-18是一种多效性的细胞因子，通过巨噬细胞，NK细胞和T细胞产生其他抗肿瘤因子加强机体对肿瘤的免疫力，在抗肿瘤，免疫调节中受到广泛关注，将在临床应用中有重要价值。本文就IL-18及其基因在肿瘤治疗中的应用进展及其部分作用机制作一综述。     

胃癌患者血清白细胞介素-6的测定及临床意义

目的探讨血清白细胞介素-6与胃癌生物学特性的关系。方法采用ELISA法(双抗体夹心酶联免疫吸附试验)检测28例胃癌患者和32例胃溃疡患者手术前后血清IL-6含量,并进行相关分析。结果胃癌患者血清IL-6水平明显高于正常人及胃溃疡患者(P<0.01),且与手术效果、临床分期和癌细胞分化程度有关(P<0.01)。结论胃癌患者血清IL-6水平在一定程度上可反映胃癌发生、发展和预后,可作为预测胃癌预后及疗效的有效指标。     

新疆地区哈萨克族、汉族男性银屑病患者骨代谢结果分析

目的探讨新疆地区哈萨克族、汉族男性寻常型银屑病患者可能存在的骨代谢结果差异及影响因素。方法入选对象为2012年1月至2017年10月在新疆生产建设兵团医院皮肤科就诊并已明确诊断的哈萨克族男性寻常型银屑病患者共112例,作为研究组。同时,根据年龄、体重等选择同期就诊且已行相关检查的112例汉族男性银屑病患者作为对照组。结果由两组患者血清Ca、P、ALP、GLU、25-OH-D_3的浓度比较可见,哈萨克族组血清Ca、ALP、25-OH-D_3明显高于汉族组,其差异具有统计学意义(P0.05)。腰椎、股骨颈及Ward三角骨密度比较,哈萨克族男性银屑病组骨密度值均略高于汉族组,其差异在L_1、L_3、L_4,但无统计学意义(P0.05),在L_2、股骨颈及ward三角具有统计学意义(P0.05)。结论哈萨克族男性银屑病患者组骨代谢水平明显高于汉族男性银屑病患者组。     

Elevated serum interleukin-18 levels might reflect the high risk of hospitalization in patients on peritoneal dialysis

BACKGROUND: Interleukin (IL)-18 is a potent pro-inflammatory cytokine and plays a central role in atherosclerotic plaque rupture and accelerates atherosclerosis. AIM: The aim of this study was to determine serum IL-18 levels in patients on peritoneal dialysis (PD) and to assess their relationship with hospitalization. METHODS: Forty-three PD patients and 20 healthy individuals were enrolled in this study. We investigated the relationship of the serum concentrations of IL-18 and other well-established atherosclerotic markers, such as asymmetric dimethylarginine (ADMA). Hospitalization data from over a 18-month period were prospectively obtained on all 43 PD patients. Classic factors were entered into a Cox regression model to predict first hospitalization. RESULTS: The serum levels of IL-18 in patients on PD were significantly higher than those of healthy individuals (228.5 +/- 140.3 pg/mL vs 154.8 +/- 44.7 pg/mL, P < 0.05, respectively). Furthermore, serum IL-18 levels showed a positive correlation with duration of PD, serum beta2 microglobulin and serum ADMA levels. Mean serum levels of IL-18 were significantly higher among patients who had experienced at least one hospitalization than those who had not (279.9 +/- 164.3 vs 158.5 +/- 43.9 pg/mL, P = 0.0426). Furthermore, the relative risk for first hospitalization for each increase in IL-18 (pg/mL) levels was associated with a 1.182 (95% confidence interval, 1.012-1.364; P = 0.0071) increase in the risk for future hospitalization events. CONCLUSION: The present study suggests the elevated serum IL-18 levels might increase the risk for future hospitalization in patients on PD.     

Higher plasma interleukin-18 levels associated with poor quality of sleep in peritoneal dialysis patients.

BACKGROUND: Sleep disorders are prevalent in patients with end-stage renal disease. Increasing evidence suggests that cytokines are involved in the regulation of sleep and wakefulness. The purpose of this study was to examine the relationship between quality of sleep and plasma interleukin-18 levels in peritoneal dialysis patients. METHODS: Plasma interleukin-18 levels were determined by the enzyme-linked immunosorbent assay (ELISA) methodology in 57 peritoneal dialysis patients. Quality of sleep was measured using the Pittsburgh Sleep Quality Index. Demographic and routine laboratory data were recorded. RESULTS: In our cohort, the poor sleepers had higher plasma interleukin-18 levels (559.16 +/- 261.22 pg/ml vs 397.49 +/- 191.81 pg/ml, P = 0.01). The plasma interleukin-18 level was positively correlated with the Pittsburgh Sleep Quality Index score (r = 0.286, P = 0.031), that is, there was a positive association between higher plasma interleukin-18 levels and poorer quality of sleep. CONCLUSION: This study demonstrates that interleukin-18 may be involved in sleep disorders in end-stage renal disease patients. Higher plasma interleukin-18 levels are associated with poorer quality of sleep in peritoneal dialysis patients. Whether a cause-and-effect relationship exists between interleukin-18 and quality of sleep deserves further study.     

Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3

Lipoprotein glomerulopathy (LPG) is a rare disease, characterized by a special histology, including dilated glomerular capillaries filled with pale-stained and meshlike lipoprotein thrombi. It always presents with proteinuria or nephrotic syndrome. Although hyperlipidemia is not always seen, most patients have type III hyperlipoproteinemia with apolipoprotein (apo) E2/3 phenotyping. Although the clinical feature of LPG is rarely described, LPG associated with other glomerulopathy, including IgA nephropathy, membranous nephropathy, and lupus nephritis, has been documented. Until now, there have been no reports of psoriasis vulgaris associated with LPG. The authors present 2 cases of LPG with apo E3/3 genotyping associated with psoriasis vulgaris. The first patient was a 65-year-old woman who presented with nephrotic syndrome with daily urinary protein loss of 9.05 g and itchy erythematous scaly plaques on her trunk and lower limbs for 1 year. The renal biopsy results showed LPG, and the skin biopsy results showed psoriasis. The second patient was a 50-year-old man with history of psoriasis over his trunk and 4 limbs for 30 years. He also presented with nephrotic syndrome with daily urinary protein loss of 7.55 g. The renal biopsy results also showed LPG. The genotype of apo E showed E3/3, and lipoprotein electrophoresis showed a type III hyperlipoproteinemia-like pattern in both cases. The authors suggest that presence of apo E3/3 genotype cannot rule out the diagnosis of type III hyperlipoproteinemia and LPG. Besides, LPG should be included in the differential diagnosis of psoriatic patients with nephrotic syndrome, especially in Asian patients who show poor response to traditional therapy. Renal biopsy should be performed to make the definitive diagnosis.     

乌鲁木齐市229例中老年寻常型银屑病患者骨代谢测定结果分析

目的探讨寻常型银屑病患者骨代谢结果的差异及影响因素。方法将229例已明确诊断的寻常型银屑病患者作为研究组,同时根据年龄、性别不同选择同期在我院体检中心进行体检的非银屑病健康体检者229例作为对照组。结果男性血清Ca、P银屑病组低于非银屑病组,Mg、ALP、TG、LDL-C男性、女性银屑病组均高于非银屑病组;银屑病组血清25-OH-D3高于非银屑病组;腰椎骨密度男性、女性非银屑病组均略高于银屑病组,男性银屑病组L_1、L_2及腰椎骨密度均值低于女性银屑病组,腰椎均值具有统计学差异;银屑病组右侧股骨颈及ward’s三角区骨密度略高于左侧;银屑病组患者按不同病程统计银屑病患者出现骨量减低及骨质疏松症大多发生于病程10~15年及5~10年组(分别占28.319%和27.876%),其次是15~20年组(占22.566%);分组统计男性组骨密度正常比例明显高于女性组(女性组占8.850%,男性组38.496%);同组内比较:男性发生骨量减低及骨质疏松症或骨折的比例占44.585%,而女性组占72.222%,明显高于男性组;女性组15~20年组及大于20年组出现骨折,共2例骨折(占2.778%),男性大于20年组出现1例骨折(占0.637%)。结论银屑病患者组骨代谢水平明显低于正常对照组,且在银屑病发病的早期即应该开始骨质疏松的预防教育。     

Macrophage-derived interleukin-18 in experimental renal allograft rejection.

BACKGROUND: Interleukin 18 (IL-18) is primarily a macrophage-derived, pro-inflammatory cytokine. As macrophages can act as effector cells in acute rejection, we examined the role of IL-18 in a rat model of acute renal allograft rejection. METHODS: Life-sustaining orthotopic DA to Lewis allograft and Lewis-Lewis isograft kidney transplants were performed. In the same model, macrophage-depleted animals, achieved with liposomal-clodronate therapy, were also studied. Macrophage (ED1+) accumulation and IL-18 expression was assessed by immunohistochemistry. CD11b+ cells (macrophages) were isolated from kidney and spleen by micro beads. Real-time PCR was used to assess IL-18 and INF-gamma mRNA expression in tissue and cell isolates. RESULTS: Allografts, but not isografts, developed severe tubulo-interstitial damage and increased serum creatinine by day 5 (P<0.001). Immunohistochemistry revealed a greater ED1+ cell accumulation in day 5 allografts compared with isografts (P<0.001). IL-18 mRNA expression was increased 3-fold in allografts compared to isografts (P<0.001). Accordingly, IL-18 protein was increased in allografts (P<0.001), and was predominantly expressed by ED1+ macrophages. CD11b+ macrophages isolated from allografts had a 6-fold upregulation of IL-18 mRNA expression compared to isograft macrophages (P<0.001). Macrophage depletion resulted in a marked attenuation of allograft rejection, ED1+ and IL-18+ cells were significantly reduced (P<0.05) as was IL-18 mRNA expression (29.28+/-2.85 vs 62.48+/-3.05, P<0.001). INF-gamma mRNA expression (P<0.01) and iNOS (P<0.001) production were also significantly reduced in the macrophage-depleted animals. CONCLUSION: This study demonstrates that IL-18 is significantly increased during acute rejection and is principally produced by intra-graft macrophages. We hypothesize that IL-18 upregulation may be an important macrophage effector mechanism during the acute rejection process.     

The role of interleukin-18 in renal injury

Interleukin (IL)-18 is a relatively new pro-inflammatory cytokine, formerly known as interferon-gamma-inducing factor, which induces interferon-gamma production in T cells and natural killer cells. It is synthesized as a biologically inactive precursor, which requires cleavage into an active molecule by an intracellular cysteine protease similar to IL-1beta. This review examines the pro-inflammatory role of IL-18 in various types of renal injury (i.e., endotoxemia, cisplatin toxicity, allograft rejection, and ischemia-reperfusion injury) and explores the integral role of IL-12 in IL-18 function and activity.     

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

Background: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). Methods: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120?mL per minute and above 120?mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. Results: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR?Conclusions: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.     

动态检测血清白介素-18对急性胰腺炎病情及预后评价的意义

目的 探索急性胰腺炎患者血清中自介素-18(IL-18)水平变化情况,及其与患者入院时APACHE Ⅱ评分及患者预后之间的关系.方法 按照急性胰腺炎的临床诊断及分级标准分组选择AP患者34例,其中重症胰腺炎(SAP)患者12例,轻型急性胰腺炎(MAP)患者22例,正常对照组16例.用ELISA法检测血清IL-18浓度.结果 血清中IL-18浓度在MAP和SAP两组患者之间均存在统计学差异(P<0.01),SAP组明显高于MAP组,且IL-18水平动态变化与APACHEⅡ评分呈正相关.结论 血清IL-18参与了急性胰腺炎的炎症反应过程,可以作为预测急性胰腺炎严重程度的指标.     

Interleukin-18 is a strong predictor of hospitalization in haemodialysis patients.

BACKGROUND: Morbidity and mortality rates are high among patients with end-stage renal disease (ESRD), and recent evidence suggests that this may be linked to inflammation. Current research has also demonstrated the crucial involvement of interleukin-18 (IL-18) in inflammation. In agreement, the activity of IL-18 has been markedly up-regulated in ESRD patients. However, it has not been established whether elevated plasma IL-18 predicts outcome in haemodialysis (HD) patients. METHODS: To determine whether plasma IL-18 predicts overall hospitalization, we studied 184 ESRD patients (62% males, 58.5+/-1.0 years of age) undergoing maintenance HD treatment. The patients were followed for 12 months and were stratified by the tertiles of plasma IL-18 levels. Classic factors, such as age, body mass index, duration of HD, nutritional and inflammatory parameters, co-morbidity, dialysis adequacy, and lipid status were entered into a Cox regression model to predict hospitalization. The Kaplan-Meier method was used to analyse the cumulative proportion of hospitalization-free events. RESULTS: Significantly different hospitalization days and frequencies (P<0.05) were observed when patients were divided according to tertiles of plasma IL-18 levels. Patients were stratified according to IL-18 tertiles and analysed separately according to the hospitalization-free period. In the Kaplan-Meier model, the upper tertile of IL-18 had the highest probability of a hospitalization event during the entire follow-up period (P log rank = 0.027). In the Cox proportional hazard model, the relative risk for first hospital admission for each increase in Ln IL-18 (pg/ml) concentration was associated with a 1.709 (95% CI, 1.114 to 2.620; P = 0.014) increase in the risk for future hospitalization events. CONCLUSIONS: The present study demonstrated a strong predictive value of elevated IL-18 levels for poor outcome in HD patients.