新生儿感染性疾病IL-6和TNF-α的水平测定

目的为探讨新生儿感染性疾病与炎性细胞因子白细胞介素-6(IL-6)和肿瘤坏死因子(TNF-a)的关系。方法采用酶联免疫吸附试验(ELISA)法对28例新生儿感染性疾病急性期和25例恢复期患儿血清进行IL-6和TNF-α的测定,并与25例正常新生儿进行比较。结果IL-6和TNF-α含量在新生儿感染急性期显著高于正常对照组,急性期显著高于恢复期,在3例死亡病例中IL-6和TNF-α水平明显高于死亡病例。结论IL-6和TNF-α是新生儿感染性疾病的重要炎症介质,其水平的高低可以反映疾病的严重程度,对估计病情、观察疗效及判断预后有一定意义。     

妊高征患者治疗前后血清TNF-α、IL-6和IL-8检测的临床意义

目的：探讨了妊高征患者治疗前后血清TNF-α、IL-6和IL-8水平的变化及意义。方法：采用放射免疫分析对36例妊高征患者进行了血清TNF-α、IL-6和IL-8水平检测并与35名正常孕妇作比较。结果：在治疗前血清TNF-α、IL-6和IL-8水平非常显著地高于正常孕妇组（P〈0．01）,经治疗后2周,血清TNF-α、IL-6和IL-8水平与正常孕妇组比较,无显著性差异（P〉0．05）。结论：炎性细胞因子TNF-α、IL-6和IL-8在妊高征的发病机理中具有重要的作用,有一定的临床价值。     

慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8检测的临床意义

目的：探讨了慢性前列腺炎患者治疗前后血清TNF-α、IL-6和IL-8水平的变化及意义。方法：应用放射免疫分析对42例慢性前列腺炎患者进行了血清TNF-α、IL-6和IL-8检测,并与35名正常健康人作比较。结果：慢性前列腺炎患者在治疗前血清TNF-α、IL-6和IL-8水平均非常显著地高于正常人组（P〈0.01）,经综合治疗后2周,除TNF-α水平与正常人比较无差异外,血清IL-6和IL-8水平与正常人比较仍有显著性差异（P〈0.05）。结论：血清TNF-α、IL-6和IL-8可能以不同的方式参与了慢性前列腺炎的发病,其检测对了解病情、指导治疗具有重要的临床价值。     

动脉粥样硬化患者血清TNF-α、IL-6和IL-8的变化及其相关性研究

用双抗体夹心ELISA，测定了45例动脉粥样硬化患者血清TNF－a、IL－6和11．－8水平，同时用酶法测定其血含量。动脉粥样硬化患者血清TNF－a、11。－6和11。－8水平均明显高于正常对照（P＜0．01），且TNF-α水平与IL－6和IL－8正相关，TNF－αa和IL－6与血清胆固醇和低密度脂蛋白均呈正相关。     

动态监测SARS病人IL-1α、IL-1β、TNFα和IL-6含量及其意义

目的 :动态监测SARS病人IL 1α、IL 1β、TNFα和IL 6含量并探讨其意义。方法 :采用酶联免疫吸附法定量检测早期、恢复期SARS病人以及出院后SARS随访者 ,一线未患SARS健康医护人员及健康体检者血清中IL 1α、IL 1β、TNFα和IL 6含量。结果 :IL 1α和IL 1β含量在早期、恢复期与其他组比较均显著升高 (P <0 0 5 )。SARS早期组TNFα均值显著高于其他组(P <0 0 0 5 ) ,SARS恢复期组均值显著高于SARS随访组、急诊等一线未患SARS组和健康对照组 (P <0 0 1)。SARS早期组IL 6均值显著高于其他各组 (P <0 0 0 5 ) ,SARS随访组与急诊等一线未患SARS组和健康对照组间均值比较 ,均有显著差异 (P <0 0 1)。结论 :SARS在发病过程中其病理损伤与细胞因子IL 1、TNFα和IL 6有关。     

尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10检测的临床意义

目的:探讨了尖锐湿疣患者治疗前后血清TNF-α、IL-6、IL-8、IL-10水平变化及意义.方法:应用RIA和ELISA对40例尖锐湿疣患者进行了血清TNF-α、IL-6、IL-8、IL-10水平检测并与35名正常健康人作比较.结果:在治疗前尖锐湿疣患者血清IL-6及IL-8低于正常对照组.TNF-α、IL-10水平均非常显著地高于正常对照组(P＜0.01),经治疗3个月后与正常对照组比较仍有显著性差异(P＜0.05).结论:检测尖锐湿疣患者血清TNF-α、IL-6、IL-8、IL-10水平的变化对疾病的治疗、预后观察有重要的临床价值.     

SARS病人TNFα、IFN和IL-6含量变化及其意义

目的 :动态监测SARS病人肿瘤坏死因子α(TNFα)、干扰素α(IFNα)、干扰素γ(IFNγ)和白细胞介素 6(IL 6)含量变化 ,并探讨其意义。方法 :采用酶联免疫吸附法定量检测早期、恢复期以及出院后SARS随访者 ,并选择在SARS防治一线工作但未感染的健康医护人员和普通健康体检者与之对照分析。结果 :SARS早期组TNFα均值高于其他各组 (P <0 .0 1) ;恢复期组显著高于随访组、一线对照组和健康对照组 (P <0 .0 1)。SARS早期组血清IFN α均值显著高于其他各组 (P <0 .0 0 1) ;恢复期组与一线对照组比较有统计学差异 (P<0 .0 5 )。SARS早期组血清IFN γ均值显著高于其他各组 (P <0 .0 1) ;恢复期组、随访组与一线对照组比较均有统计学意义 (P <0 .0 1)。SARS早期组IL 6显著高于其他各组 (P <0 .0 1) ;随访组与一线对照组和健康对照组间均值比较均有显著性差异 (P <0 .0 1)。结论 :SARS的发病机制中病理损伤与细胞因子IFN、TNFα和IL 6有关 ,IFN具有抗病毒作用     

急性胰腺炎患者血清IL-8和INF-α含量的变化

急性胰腺炎是临床常见疾病,其发病主要与胰酶消化自身组织有关.近年来,细胞因子和免疫功能紊乱与急性胰腺炎的关系日益受到重视[1].IL-8和TNF-α在机体的炎症反应过程中发挥着重要的作用,也可能与急性胰腺炎发生发展的病理过程有关[2],但目前这方面的研究尚不多见.为此,我们检测了56例急性胰腺炎患者血清IL-8和TNF-α的含量,并探讨了其在急性胰腺炎发生发展中的作用和临床意义.     

急性胰腺炎患者血清IL—8和TNF—α含量的变化

急性胰腺炎是临床常见疾病,其发病主要与胰酶消化自身组织有关。近年来,细胞因子和免疫功能紊乱与急性胰腺炎的关系日益受到重视犤１犦。IL－８和TNF－α在机体的炎症反应过程中发挥着重要的作用,也可能与急性胰腺炎发生发展的病理过程有关犤２犦,但目前这方面的研究尚不多见。为此,我们检测了５６例急性胰腺炎患者血清IL－８和TNF－α的含量,并探讨了其在急性胰腺炎发生发展中的作用和临床意义。１材料和方法１．１研究对象住院患者５６例,符合中华医学会外科学会胰腺外科学分会１９９６年第二次方案制定的急性胰腺炎临床诊断及…     

Production of tumor necrosis factor alpha, interleukin-1 alpha, and interleukin-6 during murine coccidioidomycosis.

The proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), and interleukin-6 (IL-6) were induced in mice infected with Coccidioides immitis. Analyses of the cytokine profiles of two inbred mouse strains which differ in their susceptibility to pulmonary challenge with C. immitis revealed higher levels of IL-6 in lungs from DBA/2 mice (resistant strain) than in those from BALB/c mice (susceptible strain) beginning at day 6 and continuing through day 15 postinfection. Spleen cells from both mouse strains secreted TNF-alpha, IL-1 alpha, and IL-6 in vitro in response to stimulation with killed spherules but differed in that spleen cells from the resistant strain produced increased levels of these cytokines earlier after pulmonary challenge and at increased levels throughout the course of the disease.     

Alterations of neutrophil responses to tumor necrosis factor alpha and interleukin-8 following human endotoxemia.

Interleukin-8 (IL-8), a neutrophil chemoattractant and activating cytokine, has been implicated as a proinflammatory mediator in gram-negative sepsis. In vitro data support the notion of IL-8 as an endothelial adherence inhibitor. To evaluate this issue, we infused six volunteers with reference endotoxin and measured plasma levels of IL-8, neutrophil tumor necrosis factor alpha (TNF-alpha) receptors, TNF-alpha-induced adherence to fibronectin, and neutrophil chemotaxis to IL-8 and other attractants. We found that, at 3 h postinfusion, IL-8 but not TNF-alpha plasma levels were elevated. Neutrophils had shed L-selectin (mean channel fluorescence decrease, 79 +/- 9 to 49 +/- 7; P = 0.0625) and TNF-alpha receptors (decrease in number of receptors per cell, 1,596 +/- 340 to 574 +/- 93; P = 0.004). Cells were chemotactically desensitized to IL-8. TNF-alpha-induced adherence to fibronectin was suppressed from 69% +/- 5% of the phorbol myristate acetate response to 38% +/- 7% (P = 0.0154). These findings support the notion that release of IL-8 into the vascular space may be an in vivo mechanism for suppression of neutrophil accumulation at extravascular sites. L-Selectin loss would reduce the ability of neutrophils to adhere to activated endothelial cells. The specific loss of migratory response to IL-8 would impair neutrophil delivery to areas where IL-8 was the predominant chemoattractant. Loss of TNF-alpha-induced adherence to fibronectin would blunt those responses, including production of oxidants, capacitated by adherence.     

Association study of the interleukin-1 gene complex and tumor necrosis factor alpha gene with suicide attempts

To investigate the association between four functional polymorphisms in interleukin-1 (IL-1) [IL-1 alpha -889 C/T, IL-1 beta +3953 C/T, IL-1RA (86 bp)n] and tumor necrosis factor alpha (TNFalpha) (-308A/G) genes and suicide attempts. Distribution of the aforesaid polymorphisms was analyzed in 193 suicide attempters compared with 420 unrelated healthy controls from Asturias (Northern Spain). Genotypes were determined using standard methods. No significant differences were found in genotype or in allelic distribution of IL-1 alpha, IL-1 beta, IL-1RA, or TNFalpha gene polymorphisms. No relationship was found between genotypes and the impulsivity of the suicide attempt. Estimated IL-1 haplotype frequencies were similar in both groups (likelihood ratio test=13.26, df=14, P=0.506). Our data do not suggest that genetically determined changes in the IL-1 or TNFalpha genes confer increased susceptibility to suicidal behavior.     

Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis

BACKGROUND: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-alpha)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). Objective: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. METHODS: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of >or =35% was achieved ("treatment response"). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-alpha) from patients' PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. RESULTS: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients' PBMC produced more IL-6, IL-8 and TNF-alpha than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-alpha levels were unchanged by CyA in all patients. CONCLUSIONS: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-alpha by PBMC.     

Interferon alpha induction of metallothionein in rat liver is not linked to interleukin-1, interleukin-6, or tumor necrosis factor alpha

Synthesis of metallothionein (MT) is induced by interferon-alpha (IFN-alpha) in vitro and in vivo. In addition, IFN-alpha promotes redistribution of zinc (Zn) from the plasma to the liver in mice. However, it is not clear if IFN-alpha induces hepatic MT synthesis directly or indirectly via liberation of other cytokines. In order to address this issue, we determined hepatic MT levels, Zn concentration in plasma, liver, and urine, and plasma levels interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFalpha) in rats following intramuscular injection of human IFN-alpha (1.5 x 10(6) UI/m(2)). Animals were housed in metabolic cages and sacrificed at various times after IFN-alpha administration. Zn concentrations in serum, urine, and hepatic tissue were determined by atomic absorption spectrophotometry. MT protein was measured using the MT silver saturation method and expression of MT-1 and MT-2 mRNA was measured by RT-PCR. Plasma levels of rat IL-1, IL-6, and TNFalpha were determined using an ELISA method. Hepatic MT levels began to increase at 2 h following IFN-alpha administration and reached maximum levels at 12 h post-treatment. Induction of MT gene expression was confirmed by increases in MT-1 and MT-2 mRNA levels 6, 12, and 18 h after IFN-alpha administration. IFN-alpha treatment also resulted in biphasic increases in hepatic Zn, with levels peaking at 2 h, the time-point when MT levels are first increased, and again at 18 h. Concurrently, there were decreases in serum Zn levels at these time points, suggesting IFN-alpha induced movement of Zn from the blood to hepatic tissue. The decrease in serum Zn was not due to increased excretion since urinary Zn levels were unaffected following IFN-alpha treatment. IFN-alpha administration had no effect on plasma IL-1, IL-6, and TNFalpha levels. These results show that IFN-alpha promotes the increase of hepatic MT levels and plasma/liver redistribution directly, without IL-1, IL-6, or TNFalpha participation.     

Differential elevation of circulating interleukin-1 beta, tumor necrosis factor alpha, and interleukin-6 in AIDS-associated cachectic states.

Elevation of serum interleukin-1 beta (IL-1 beta) levels, and to a lesser degree tumor necrosis factor alpha levels, was found in cachectic human immunodeficiency virus (HIV)-infected African patients without concurrent opportunistic infection or neoplasia (HIV wasting syndrome). A heterogeneous pattern of elevations of cytokine levels, including mild elevations of IL-1 beta and pronounced elevations of IL-6 levels, was found in other cachectic states.     

High serum interleukin-10 and tumor necrosis factor alpha levels in chronic paracoccidioidomycosis

In patients with chronic paracoccidioidomycosis (n = 10), levels of tumor necrosis factor alpha, interleukin-10, and interleukin-2 in serum, measured by enzyme-linked immunosorbent assay (in picograms per milliliter, as mean +/- standard error of the mean), were higher than in normal controls (n = 8): 186 +/- 40 versus 40 +/- 7 (P < 0.05), 203 +/- 95 versus 20 +/- 8 (P = 0.001), and 96.3 +/- 78.57 versus 1.19 +/- 1.19 (P = 0.045), respectively. Gamma interferon and interleukin-4 levels were similar in patients and controls.     

Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes.

Purified cell walls representing a wide variety in teichoic acid and peptidoglycan structure prepared from eight different gram-positive bacterial species induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 from human monocytes in the presence of 10% plasma or serum. Significant amounts of cytokines began to be produced at concentrations above 100 ng to 1 microgram of cell walls per ml, with maximal production requiring 10 to 100 micrograms of cell wall material per ml. In the absence of plasma, the cytokine-inducing capacity of cell wall preparations was lower by at least an order of magnitude. The serum-derived cofactor was inactivated by heating at 90 degrees C for 30 min, suggesting that the activity is associated with a protein. On the other hand, replacement of normal with hypogammaglobulinemic plasma, inactivation of complement (at 56 degrees C), and blockade by the monoclonal antibody MY4 of the CD14 receptors on monocytes did not inhibit the production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha in the presence of polymyxin B, and macrophages derived from the lipopolysaccharide-insensitive cell line of C3He/HeJ mice also produced this cytokine when stimulated by cell walls. Both peptidoglycan and the soluble glycan-teichoic acid component prepared by an enzymatic method from the same wall preparation exhibited a serum-dependent induction of TNF-alpha from monocytes, while stem peptides and disacharride peptides had only poor, if any, activity. Cell walls may contribute to the septic shock induced by gram-positive bacteria.     

Anomalous role of tumor necrosis factor alpha in experimental enterococcal infection

The murine D-galactosamine (D-gal) model of tumor necrosis factor alpha (TNF-alpha) hypersensitization was used as an initial tool to investigate the potential contribution of TNF-alpha to lethal intraperitoneal (i.p.) infection with Enterococcus faecalis. D-gal sensitized mice to lethal E. faecalis infection, whereas dexamethasone and neutralizing anti-TNF-alpha antibody protected D-gal-treated, E. faecalis-infected mice, implicating TNF-alpha in the lethal response to E. faecalis infection in D-gal-treated mice. Circulating TNF-alpha was undetectable for at least 8 h following i.p. E. faecalis infection, although low peritoneal levels of TNF-alpha were detected within 3 h, suggesting that localized TNF-alpha production contributed to the lethal response to E. faecalis infection in D-gal-treated mice. Although i.p. E. faecalis infection failed to induce a detectable systemic TNF-alpha response, circulating Interleukin-6 (IL-6) was detected within 3 h of infection. IL-6 was also detected in the peritoneum within an hour of infection, prior to the appearance of peritoneal TNF-alpha. In striking contrast to in vivo results, E. faecalis induced a potent and rapid TNF-alpha response from both mouse peritoneal macrophages and the RAW 264.7 cell line in vitro. This led us to hypothesize that TNF-alpha production in response to E. faecalis infection is suppressed by IL-6 in vivo. In vitro experiments demonstrated a statistically significant, but modest, inhibitory effect of IL-6 on TNF-alpha production by RAW cells stimulated with E. faecalis. Collectively, these data indicate that acute, lethal E. faecalis infection appears to induce an unusual cytokine response that differs in character from that previously described for most other gram-positive and gram-negative bacteria.     

Production of human tumor necrosis factor alpha, interleukin-6, and interleukin-10 is induced by lactic acid bacteria.

To investigate the role of cytokines in interactions between lactic acid bacteria and the immune system, we measured production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-10 from human peripheral blood mononuclear cells after stimulation with live or glutaraldehyde-fixed bacteria. Production of tumor necrosis factor alpha, IL-6, and, in some cases, IL-10 was induced in amounts even greater than those obtained with lipopolysaccharide as a stimulant. Our results suggest that lactic acid bacteria can stimulate nonspecific immunity.