小儿细菌性肺炎支气管肺泡灌洗液IL-6及IL-8变化的探讨

目的探讨支气管肺泡灌洗液（BALF）中白细胞介素（IL）-6、IL-8与小儿细菌性肺炎的相关性。方法采用双抗体夹心ELISA法分别测定26例细菌性肺炎患儿（肺炎组）治疗前后和14例无明显气道炎性反应患JL（对照组）BALF中IL-6、IL-8水平，并行中性粒细胞（PMN）和肺泡巨噬细胞（AMs）计数。结果肺炎组治疗前BALF中IL-6和IL-8水平、细胞总数、PMN明显比治疗后及对照组高（P〈0．01）。革兰阴性细菌感染患儿BALF中IL-6、IL-8水平比革兰阳性细菌感染显著升高（P〈0．01）。肺炎组BALF中IL-6水平与AMs呈显著正相关（r=0．7615，P〈0．01），肺炎组BALF中IL-8水平分别与PMN和AMs呈显著正相关（r=0．8956，r=0．6018，P〈0．01）。结论IL-6、IL-8参与小儿细菌性肺炎的炎性反应，BALF中IL-6和IL-8水平动态变化对评价小儿细菌性肺炎的病情有一定的临床意义。     

小儿细菌性肺炎支气管肺泡灌洗液IL-6及IL-8变化的探讨

目的 探讨支气管肺泡灌洗液(BALF)中白细胞介素(IL)-6、IL-8与小儿细菌性肺炎的相关性.方法 采用双抗体夹心ELISA法分别测定26例细菌性肺炎患儿(肺炎组)治疗前后和14例无明显气道炎性反应患儿(对照组)BALF中IL-6、IL-8水平,并行中性粒细胞(PMN)和肺泡巨噬细胞(AMs)计数.结果 肺炎组治疗前BALF中IL-6和IL-8水平、细胞总数、PMN明显比治疗后及对照组高(P<0.01).革兰阴性细菌感染患儿BALF中IL-6、IL-8水平比革兰阳性细菌感染显著升高(P<0.01).肺炎组BALF中IL-6水平与AMs呈显著正相关(r=0.7615.P<0.01),肺炎组BALF中IL-8水平分别与PMN和AMs呈显著正相关(r=0.8956,r=0.6018,P<0.01).结论 IL-6、IL-8参与小儿细菌性肺炎的炎性反应,BALF中IL-6和IL-8水平动态变化对评价小儿细菌性肺炎的病情有一定的临床意义.     

环境细颗粒物亚慢性染毒对大鼠炎症损伤及免疫功能的影响研究

目的建立细颗粒物的亚慢性暴露动物模型,探讨PM2.5对大鼠炎症损伤及免疫功能的影响。方法应用气管滴注建立细颗粒物的亚慢性暴露动物模型;光镜下观察各脏器病理学变化;采用相应的试剂盒测定肺泡灌洗液中的总蛋白和唾液酸水平;ELISA方法检测细胞因子IL-6和TNF-α水平,采用RT-PCR方法检测肺组织中这两种细胞因子的表达水平;收集肺泡巨噬细胞,采用孔雀绿比色法检测巨噬细胞的吞噬功能;取脾脏,采用MTT方法检测淋巴细胞的增殖功能。结果在染毒后的大鼠肺内均观察到异物性肉芽肿形成;在肝脏血窦内观察到有单核吞噬细胞聚集形成肉芽肿的趋势;在肺门淋巴结和肝脏、肾脏血管内观察到明显的吞噬PM2.5的巨噬细胞和游离的PM2.5。总蛋白和唾液酸水平随着暴露时间和剂量升高而增加。在观察的前3个月,染毒组TNF-α表达水平逐渐升高,而在6个月时,TNF-α水平明显降低;IL-6表达水平随着染毒剂量的增加而升高,并呈现明显的剂量-效应关系,染毒3个月后最高,而在6个月后表达水平回落。肺泡巨噬细胞的吞噬功能随着剂量的增加而下降。淋巴细胞增殖功能没有出现显著性变化。结论细颗粒物的亚慢性暴露可以引起机体的持续炎症损伤;细颗粒物对免疫系统的损伤随着剂量和暴露时间的增加而增加,细颗粒物引起的细胞因子网络紊乱会加重免疫系统的损伤;细颗粒物引起巨噬细胞吞噬功能下降,是肺部慢性疾病的致病机制之一。     

Mycobacterium terrae isolated from indoor air of a moisture-damaged building induces sustained biphasic inflammatory response in mouse lungs

Occupants in moisture-damaged buildings suffer frequently from respiratory symptoms. This may be partly due to the presence of abnormal microbial growth or the altered microbial flora in the damaged buildings. However, the specific effects of the microbes on respiratory health and the way they provoke clinical manifestations are poorly understood. In the present study, we exposed mice via intratracheal instillation to a single dose of Mycobacterium terrae isolated from the indoor air of a moisture-damaged building (1 X 10(7), 5 X 10(7), or 1 X 10(8) microbes). Inflammation and toxicity in lungs were evaluated 2 hr later. The time course of the effects was assessed with the dose of 1 X 10(8) bacterial cells for up to 28 days. M. terrae caused a sustained biphasic inflammation in mouse lungs. The characteristic features for the first phase, which lasted from 6 hr to 3 days, were elevated proinflammatory cytokine [i.e., tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)] levels in the bronchoalveolar lavage fluid (BALF). TNF-alpha was produced in the lungs more intensively than was IL-6. Neutrophils were the most abundant cells in the airways during the first phase, although their numbers in BALF remained elevated up to 21 days. The characteristics of the second phase, which lasted from 7 to 28 days, were elevated TNF-alpha levels in BALF, expression of inducible nitric oxide synthase in BAL cells, and recruitment of mononuclear cells such as lymphocytes and macrophages into the airways. Moreover, total protein, albumin, and lactate dehydrogenase concentrations were elevated in both phases in BALF. The bacteria were detected in lungs up to 28 days. In summary, these observations indicate that M. terrae is capable of provoking a sustained, biphasic inflammation in mouse lungs and can cause a moderate degree of cytotoxicity. Thus, M. terrae can be considered a species with potential to adversely affect the health of the occupants of moisture-damaged buildings.     

Acute alcohol intake impairs lung inflammation by changing pro- and anti-inflammatory mediator balance.

Previous studies have shown that alcohol (ethanol [EtOH]) intoxication impairs lung immunity by affecting cytokines pivotal to the inflammatory process. The objective of this study was to test the hypothesis that acute alcohol intoxication impairs lung innate immunity by downregulating the expression of proinflammatory mediators while simultaneously upregulating anti-inflammatory mediators. EtOH was administered to the mice 0.5h prior to an intratracheal injection of Escherichia coli lipopolysaccharide (LPS). The animals were killed either 4 or 24h after LPS to recover plasma, lungs, and bronchoalveolar lavage fluid. Lung inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), IL-6, macrophage inhibitory factor (MIF), IL-10, TGF-beta, and receptors for TNF-alpha, IL-1beta, IL-6, and TGF-beta as well as glycoprotein (gp)130 and corticosterone (CS) levels were evaluated at mRNA and protein level. While the mRNA expression and the soluble TNF-Rp55 levels were significantly upregulated by EtOH, LPS-induced TNF-alpha activity, TNF-Rp55 mRNA expression, and soluble TNF-Rp55 levels were significantly suppressed. The LPS-induced expression of IL-1beta, IL-6, MIF, gp130, and receptors IL-1RI, IL-1RII, and IL-6Ralpha were also significantly impaired by EtOH. EtOH increased significantly the basal IL-10 activity at 3h, which continued to remain elevated even at 24h. The EtOH effect on IL-10 activity persisted even in LPS-challenged mice. EtOH and LPS augmented lung CS levels independently of each other. EtOH suppressed upregulation of TGF-beta1 mRNA expression by LPS and blocked completely LPS-induced TGF-beta1 secretion. In conclusion, the data suggest that the suppression of acute lung inflammation by EtOH intoxication is largely due to impairment by EtOH of proinflammatory cytokine signaling at the levels of cytokine expression and secretion as well as receptor expression and soluble receptor activity. The augmentation by EtOH of anti-inflammatory mediators' secretion most likely shifts the cytokine balance in the anti-inflammatory direction.     

Dietary alpha-linolenic acid inhibits proinflammatory cytokine production by peripheral blood mononuclear cells in hypercholesterolemic subjects

BACKGROUND: Atherosclerosis is a chronic inflammatory disease. We previously reported that a diet high in alpha-linolenic acid (ALA) reduces lipid and inflammatory cardiovascular disease risk factors in hypercholesterolemic subjects. OBJECTIVE: The objective was to evaluate the effects of a diet high in ALA on serum proinflammatory cytokine concentrations and cytokine production by cultured peripheral blood mononuclear cells (PBMCs) from subjects fed the experimental diets. DESIGN: A randomized, controlled, 3-diet, 3-period crossover study design was used. Hypercholesterolemic subjects (n = 23) were assigned to 3 experimental diets: a diet high in ALA (ALA diet; 6.5% of energy), a diet high in linoleic acid (LA diet; 12.6% of energy), and an average American diet (AAD) for 6 wk. Serum interleukin (IL)-6, IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) concentrations and the production of IL-6, IL-1beta, and TNF-alpha by PBMCs were measured. RESULTS: IL-6, IL-1beta, and TNF-alpha production by PBMCs and serum TNF-alpha concentrations were lower (P < 0.05 and P < 0.08, respectively) with the ALA diet than with the LA diet or AAD. PBMC production of TNF-alpha was inversely correlated with ALA (r = -0.402, P = 0.07) and with eicosapentaenoic acid (r = -0.476, P = 0.03) concentrations in PBMC lipids with the ALA diet. Changes in serum ALA were inversely correlated with changes in TNF-alpha produced by PBMCs (r = -0.423, P < 0.05). CONCLUSIONS: Increased intakes of dietary ALA elicit antiinflammatory effects by inhibiting IL-6, IL-1beta, and TNF-alpha production in cultured PBMCs. Changes in PBMC ALA and eicosapentaenoic acid (derived from dietary ALA) are associated with beneficial changes in TNF-alpha release. Thus, the cardioprotective effects of ALA are mediated in part by a reduction in the production of inflammatory cytokines.     

Polymorphisms of the IL-1 gene complex in coal miners with silicosis

BACKGROUND: Silicosis is characterized by fibrosing nodular lesions that eventually develop into progressive pulmonary fibrosis. Pro-inflammatory cytokines, such as interleukin-1 (IL-1), play a key role in the development of silicosis by regulating mediators which are responsible for lung injury, inflammation, and potentially fibrosis. To study whether functional single nucleotide polymorphisms (SNPs) located in the regulatory elements of genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist (RA) cytokines are associated with silicosis, we examined 318 Caucasian cases confirmed histopathologically with pulmonary silicosis and 163 controls without any apparent inflammation or other pulmonary disease. METHODS: Genotyping was carried out by polymerase chain reaction-restriction fragment length polymorphism technique. RESULTS: The proportion of the IL-1RA (+ 2018) allele 2 genotype was increased in miners with silicosis (0.27) compared to controls (0.16). The odds of being a case were 2.15 (CI = 1.4-3.3) times higher for subjects with at least one copy of allele 2. No statistically significant differences in the allelic frequencies or genotype distributions for IL-1alpha (+ 4845) or IL-1beta (+ 3953) were found between the control and disease groups. CONCLUSIONS: This is the first report showing an association between the IL-1RA (+ 2018) polymorphism and silicosis, and suggests that this polymorphism may confer increased risk for the development of the disease.     

大气混合污染物对大鼠肺组织CC16及细胞因子的影响

目的测定大气污染物对大鼠肺组织CC16、TNF-α和IL-6的mRNA表达影响。方法用日本产低流量PM10空气采样器采集PM10颗粒物,采样滤膜用生理盐水超声震荡洗脱,混悬液定容为15mg/ml。48只体重为200~240g Wistar大鼠随机分为3个实验组和1个对照组。实验组大鼠分别气管注入15mg/ml PM10的生理盐水混悬液1ml,对照组大鼠注入1ml生理盐水。次日,实验组大鼠静态吸入浓度分别为15、12、400mg/m3的SO2、NO2、CO空气混合气,每天吸入2h,对照组吸入正常空气。于吸入气体污染物1天、7天和30天后次日分别处死实验组和对照组大鼠,取肺组织,采用RT-PCR方法测定TNF-α、IL-6和CC16的mRNA表达水平;采用免疫组化和Western blotting测定肺和BALF中CC16的水平。结果吸入大气污染物组在吸入后1天和7天其肺组织CC16 mRNA的表达量明显低于对照组;细胞因子TNF-α和IL-6 mRNA表达增强,高于对照组,并于染毒初期即染毒第1天和第7天增高明显,染毒第30天,又呈下降趋势。免疫组化检测显示,实验组大鼠肺组织CC16表达水平在染毒后1天,7天时显著高于对照组,而在30天时低于对照组。BALF中CC16表现为1天和7天时显著低于对照和30天组。结论大气污染物作用于大鼠呼吸系统后,大鼠肺组织和BALFCC16表达量下降,TNF-α和IL-6 mRNA表达增强,并且在污染物作用早期变化明显。     

Melatonin induces changes to serum cytokines in mice infected with the Venezuelan equine encephalomyelitis virus

We determined the influence of melatonin (MLT) on the induction of interleukin (IL)-2, IL-1 beta, IL-4, tumour necrosis factor-alpha (TNF-alpha) and gamma interferon (IFN-gamma) on mice infected with the Venezuelan equine encephalomyelitis (VEE) virus. Levels of IFN-gamma in the MLT-treated group were significantly increased (P < 0.001) when compared with the control non-infected group from day 1 to 6 post-infection (p.i.), while in infected mice treated with 500 micrograms MLT/kg of bodyweight enhanced levels of IFN-gamma were evident from 4 to 6 days p.i. No differences were detected in the levels of IL-2 between the controls, the infected mice treated with MLT and the infected untreated group, from day 2 p.i. No changes in serum levels of IL-4 were detected. In infected mice treated with MLT, blood levels of IL-1 beta were elevated almost 10-fold from day 1 to day 6 p.i. when compared to the control, the infected and the non-infected MLT-treated mice (P < 0.001). A highly significant rise (P < 0.001) of TNF-alpha was found in infected mice treated with MLT, from day 1 to 6 p.i. when compared to the other groups. A significant rise (P < 0.001) was also evident in the infected non-MLT-treated group and a less pronounced rise in the non-infected mice treated with MLT when compared to controls. The blockade of IFN-gamma and TNF-alpha did not inhibit the protective effect of MLT but when IL-1 beta was neutralized, 100% of the infected mice died suggesting that IL-1 beta induced by MLT treatment is a target cytokine to generate an immune response against the viral infection.     

Anti-Inflammatory Properties of Fructo-Oligosaccharides in a Calf Lung Infection Model and in Mannheimia haemolytica-Infected Airway Epithelial Cells

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.     

Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity

OBJECTIVE: We previously reported elevated serum levels of the cytokines interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with anorexia nervosa (AN). We investigated the cellular production of these two cytokines and of interferon-gamma (IFN-gamma), interleukin-1alpha (IL-1alpha), and tumor necrosis factor-alpha (TNF-alpha) in subjects with AN, bulimia nervosa (BN), and obesity as well as in normal-weight control subjects. METHODS: Supernatant fluids from isolated peripheral blood mononuclear cells (PBMC) incubated with and without concanavalin A (ConA) were assayed for cytokine concentrations by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant differences across the four groups were found in the stimulated cellular production of IFN-gamma and IL-6. Stimulated IFN-gamma production was elevated in the AN group compared to controls. IL-6 production was significantly elevated in obese subjects relative to the two normal-weight groups, BN and controls, and tended to be higher in the AN group than in the controls, but not significantly so. IL-1alpha production was greater in obese subjects. CONCLUSION: The findings of increased IFN-gamma production and a tendency toward increased IL-6 production (both of which suppress food intake in animals) in individuals who severely restrict food intake suggest a potential role for these cytokines in the pathogenesis of AN. Elevated IL-6 and IL-1alpha production by PBMC in obese individuals requires further investigation to determine if these cytokines contribute to the development or perpetuation of obesity.     

Study on proinflammatory cytokines (IL-1 beta, IL-6, TNF-alpha) and IL-2 in patients with acute hepatitis B.

Cytokine production in patients with hepatitis B may be related either to multiple immune abnormalities or to favourable outcome of the disease. Serum levels of IL-1 beta, IL-2, IL-6 and TNF-alpha were determined dynamically by ELISA kits in patients with self-limited form of acute hepatitis B infection (A-HBV) during the first, second and third decade after icterus appearance. IL-1 beta, IL-6 and TNF-alpha had characteristically high levels in patients measured in all decades, but these were the highest during the first. Then they gradually decreased, reaching normal values at the stage of convalescence. Serum IL-2 levels were found to be most significantly elevated during the second decade and also dropped to normal values in the course of the disease. Patients who cleared HBsAg on the third month after dehospitalisation had higher mean values of IL-2, IL-6 and TNF-alpha in comparison with those who were still HBsAg carriers, thus indicating that proinflammatory cytokine production in self-limited HBV may be important for viral clearance.     

白介素-8与急性呼吸窘迫综合征

白细胞介素8(IL-8)是由多种细胞合成与分泌的一种细胞因子,具有很强的中性粒细胞化学趋化作用.急性呼吸窘迫综合征(ARDS)患者的血清及支气管肺泡灌洗液(BALF)中IL-8水平均明显升高,它参与了肺内白细胞的募集、活化以及黏附分子的表达,在ARDS发病机制中起着重要作用.     

Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets

Cytokines play a central role in immune cell response, but they also participate in the maintenance of tissue integrity. Changes in the cytokine network of the pig gut may be expected at weaning, because abrupt changes in dietary and environmental factors lead to important morphological and functional adaptations in the gut. This study measured the gene expression of 6 inflammatory cytokines along the small intestine (SI) and the proximal colon in 28-d-old piglets (n = 45) at different time points (0, 1, 2, 5 and 8 d) postweaning, using RT-PCR. Villus-crypt architecture and enzymatic activities of lactase and sucrase in the SI were also examined. The results confirmed that weaning is associated with morphological and enzymatic changes in the SI. In addition, the data indicated that cytokine response in the gut could be divided into two periods: an early acute response (0 to 2 d postweaning) and a late long-lasting response (2 to 8 d postweaning). Between d 0 and d 2, the levels of IL-1beta, IL-6, and TNF-alpha messenger RNA (mRNA) increased. Marked upregulation of IL-1beta mRNA occurred in most parts of the intestine, whereas IL-6 and TNF-alpha mRNA markedly increased only at specific sites in the intestine. Between d 2 and d 8, the levels of IL-1beta, IL-6, and TNF-alpha mRNA rapidly returned to preweaning values, except that the level of TNF-alpha mRNA remained high in the distal SI. Levels of IL-12 subunit p40 (IL-12p40) and IL-18 mRNA also decreased, compared to those on d 0. Taken together, these results demonstrate that weaning in piglets is associated with an early and transient response in gene expression of inflammatory cytokines in the gut.     

血红素氧合酶-1激活对大鼠化学性急性呼吸窘迫综合征的防治作用及其机制

目的探讨血红素氧合酶1(HO1)激活对化学性急性呼吸窘迫综合征(ARDS)的防治作用及其可能机制。方法利用HO1的作用底物———血红蛋白(Hb)诱导HO1的产生,并用免疫印迹法(Westernblot)和逆转录聚合酶链反应(RTPCR)等方法验证其蛋白量和mRNA表达情况;采用酶联免疫吸附试验(ELISA)检测油酸型ARDS大鼠血清及支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNFα)和白细胞介素8(IL8)水平;结合动脉血气分析、肺湿重、干重测定和病理学检查等方法来验证HO1激活对ARDS的防治效果。结果Westernblot测定结果证实24h时HO1蛋白明显增加,RTPCR结果表明其mRNA表达在16h就已明显升高;且Hb+油酸(OA)组ARDS大鼠血清和BALF中TNFα及IL8水平明显低于OA组,差异有统计学意义(P<0.01)。Hb+OA组动脉血PaO2[(56.28±6.71)mmHg]、血氧饱和度(79.53%±5.82%)及血氧合指数[(258.81±29.37)mmHg]均明显高于OA组[分别为(35.08±4.59)mmHg、55.80%±12.76%、(167.86±21.94)mmHg],肺湿干重和病理学检查指标亦有明显改善。结论Hb可成功地诱导体内HO1的表达,并显示出防治ARDS的作用;其机制可能系HO1通过减少炎症细胞因子如TNFα和IL8来减轻肺损伤。     

Effect of tumor weight and tube feeding on TNF-alpha and IL-1beta mRNA expression in the brain of mice.

BACKGROUND: Previous studies have shown that cytokine mRNA expression is elevated in the brains of anorectic, tumor-bearing rats. The objectives of the current study were as follows: (1) to determine whether a small tumor would result in up-regulation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta mRNA expression in the brain and other tissues of tumor-bearing mice; and (2) to determine whether hyperalimentation by tube feeding would prevent up-regulation of cytokine mRNA expression in the brain and other tissues of tumor-bearing mice. METHODS: Male C57BL/6 mice were divided into 4 groups: (1) control mice fed ad libitum (Control); (2) tumor-bearing mice fed ad libitum (TB); (3) control mice receiving tube feeding (CTF); and (4) tumor-bearing mice receiving tube feeding (TBTF). RESULTS: TNF-alpha and IL-1beta mRNA expression was elevated in the brains of mice with a 1% body weight tumor, relative to the control and CTF groups, without any detectable changes in the other organs. On the other hand, TNF-alpha and IL-1beta mRNA expression was elevated in all organs of mice with an 8% body weight tumor, relative to the control and CTF groups. Tube feeding did not change TNF-alpha and IL-1beta mRNA expression in mice burdened with either a 1% or 8% body weight tumor. CONCLUSIONS: Up-regulation of cytokine mRNA synthesis occurs earlier in the brain than in other organs, and hyperalimentation does not change cytokine mRNA expression in tumor-bearing mice.     

职业性慢性铅中毒患者T细胞亚群及Th1/Th2细胞因子的变化

目的初步探索职业性慢性铅中毒患者T淋巴细胞亚群及Th淋巴细胞因子的变化特点。方法对23例职业性慢性铅中毒患者（铅中毒组）及20例健康非职业铅接触成人（对照组）采用流式细胞技术检测外周静脉血淋巴细胞CD3、CD4、CD8的表达，同时通过流式细胞微球芯片捕获技术检测血浆IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ的浓度。结果铅中毒患者外周静脉血CD4相对百分比（32．68％±11．54％）及CD4／CD8比值（0．89±0．39）与对照组比较，明显下降，差异有统计学意义（P〈0．05）；血浆IL-2浓度为（2．00±0．68）pg／ml，与对照组比较明显上升，差异有统计学意义（P〈0．05）；血浆IL-10和IFN-γ浓度分别为（1．83±0．85）pg／ml和（3．42±0．85）pg／ml，与对照组比较明显减低，差异有统计学意义（P〈0．05）。结论T淋巴细胞亚群及细胞因子对评价铅免疫毒性有进一步研究价值。     

Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners

Silicosis is a fibrotic lung disease produced by the inhalation and deposition of silica dust. The association between silicosis and pulmonary tuberculosis (PTB) has been well established. Cytokines participate in the development and progression of silicosis and PTB. Functional polymorphisms in cytokine genes have been identified that alter cytokine production. The aims of the current investigation were to determine whether functional polymorphisms in the tumor necrosis factor-alpha (TNF-alpha) gene at position -308; in the transforming growth factor-beta 1 (TGF-beta1) gene at positions -509, +869 (codon 10), and +915 (codon 25); in the interleukin-10 (IL-10) gene at position -1,082, -819 and -592; and in the intron 1 of the interferon-gamma (IFN-gamma) gene at position +874 are associated with silicosis and PTB. We conducted a case-control study with 183 silicosis patients and 111 silica-exposed miners, and a 1:2 matched case-control study of 61 PTB cases and 122 PTB-free miners. Genotype analysis was performed on genomic DNA, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. There was complete linkage disequilibrium (LD) between the -819C and -592C alleles of the IL-10 gene. The genotype frequencies were similar between cases and control subjects for all investigated cytokine polymorphisms (p>0.05). We did not find an association between the different genotypes and severity of silicosis. We assume that these genetic variants do not play a dominant role in silicosis and PTB in our Chinese population.     

Characterization of clinical tolerance to inhaled zinc oxide in naive subjects and sheet metal workers

Clinical tolerance to the acute effects of zinc oxide inhalation develops in workers during periods of repeated exposure. The aims of this study were to determine whether clinical tolerance is accompanied by a reduction in the acute pulmonary inflammatory and cytokine responses to zinc oxide exposure and whether tolerance can be demonstrated in sheet metal workers who chronically inhale low levels of zinc oxide. Naive (never-exposed) subjects inhaled 5 mg/m3 zinc oxide on 1 or 3 days and underwent bronchoalveolar lavage 20 hours after the final exposure. Sheet metal workers inhaled zinc oxide on 1 day and control furnace gas on another day. Among naive subjects in whom tolerance was induced, bronchoalveolar lavage fluid percent neutrophils and interleukin-6 (IL-6) levels were significantly decreased compared with subjects who underwent only a single exposure. Sheet metal workers were much less symptomatic, but they still experienced a significant increase in plasma IL-6. The results indicate that clinical tolerance to zinc oxide is accompanied by reduced pulmonary inflammation and that chronically exposed sheet metal workers are not clinically affected by exposure to zinc oxide fume at the Occupational Safety and Health Administration Permissible Exposure Limit. The increase in IL-6 levels observed in the clinically responsive, and to a lesser extent, tolerant, states following zinc oxide inhalation is consistent with the dual role of IL-6 as a pyrogen and anti-inflammatory agent.