幽门螺杆菌相关胃炎中TNF-α和IL-1β分泌的原位研究

目的 :原位检测幽门螺杆菌 (Hp)感染时胃黏膜活检标本中肿瘤坏死因子 α(TNF α)和白介素 1 β(IL 1 β)的产生情况。方法 ;采集 1 3例Hp阴性受检者和 32例Hp阳性受检者的胃黏膜活检标本 ,通过放免法、免疫组织化学法观察并比较两组胃黏膜活检标本中细胞因子TNF α和IL 1 β的产生。结果 :胃黏膜活检标本中TNF α和IL 1 β的分泌在Hp阳性组显著高于Hp阴性组 (P <0 .0 1 ) ,但其分泌与胃黏膜的病理分型似无显著相关性 (P >0 .0 5)。TNF α和IL 1 β的组织表达在Hp阳性组也显著高于Hp阴性组 (P <0 .0 5)。结论 :Hp感染可以使局部细胞因子TNF α和IL 1 β产生增加 ,可能在Hp相关胃炎中起致病作用     

核因子-κB反义寡核苷酸对系膜细胞炎症因子基因表达的影响

目的 :探讨NF κB反义寡核苷酸 (oligodeoxynucleotide ,ODN)对人肾小球系膜细胞炎症因子表达的影响 ,为利用NF κB反义ODN治疗肾小球炎性病变奠定基础。　 方法 :人工合成p65反义、正义及错配ODN并行全程硫代磷酸化修饰。应用核酸酶保护法观察阳离子脂质体介导的不同浓度的反义ODN(0 0 0 1、0 0 1、0 1、1、1 0μmol/L)对系膜细胞TNF α、IL 1α、IL 1 β、MCP 1、IL 8、TGF β1mRNA表达的影响 ,以正义ODN(1 0 μmol/L)及错配ODN(1 0 μmol/L)作为对照组。　 结果 :正常培养状态下 ,系膜细胞可组成型表达TNF α、IL 1 β、IL 8和TGF β1mRNA ,而不表达IL 1α和MCP 1mRNA。细菌脂多糖 (lipopolysaccharide,LPS)刺激后上述 6种炎症因子表达显著上调。p65反义ODN可呈剂量依赖性地抑制LPS诱导的系膜细胞炎性细胞因子TNF α ,IL α,IL 1 β,MCP 1和IL 8的基因表达 ,而对TGF β1无显著抑制作用 ;p65正义及错配ODN均不能抑制炎性细胞因子的表达。　 结论 :p65反义ODN可明显抑制LPS诱导的肾小球系膜细胞炎性细胞因子的表达 ,提示NF κB在肾小球疾病进展中起关键性调控作用 ,其反义ODN有可能应用于肾脏病变的实验性治疗之中     

心力衰竭患者炎性与抗炎性细胞因子表达的平衡失调

目的 :了解炎性与抗炎性细胞因子在充血性心力衰竭 (CHF)过程中的变化及其临床意义。方法 :用双抗体夹心ELISA法测定 12 2例CHF患者及 30例健康人血浆中肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的浓度。结果 :①CHF患者血浆中TNF α水平明显高于对照者 (P <0 .0 5或 <0 .0 1) ,且随着心力衰竭程度的加重 ,TNF α水平呈进行性增高 ;CHF患者血浆IL 6及IL 10水平 ,心功能Ⅲ、Ⅳ级者明显高于对照者 (P <0 .0 5或 <0 .0 1) ,而心功能Ⅱ级者与对照者相比差异无显著性意义。②TNF α与IL 6 (r =0 .6 18,P <0 .0 1)、IL 10 (r =0 .5 6 6 ,P <0 .0 1)均呈正相关 ,但TNF α与IL 10的比率 (TNF α/IL 10 )也随着心功能的恶化而升高 ,IL 10的升高与TNF α的升高相比明显不足。结论 :细胞因子的变化与心力衰竭的严重程度密切相关 ,CHF患者血中炎性细胞因子明显升高的同时伴有抗炎性细胞因子升高的相对不足 ,炎性与抗炎性细胞因子之间的平衡失调可能参与了CHF的发生发展     

多器官功能障碍综合征血清炎性细胞因子变化的意义

目的 :探讨多器官功能障碍综合征 (MODS)血清炎性细胞因子的变化的意义。方法 :采用双抗体夹心酶联免疫吸附法测定 42例MODS和 3 0例健康对照组的血清肿瘤坏死因子 (TNF α)、白介素 1β(IL 1β)与白介素 6(IL 6)含量。结果 :MODS血清TNF α、IL 1β与IL 6含量 (各为2 77.64±5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L)明显高于对照组 ( 2 3 .3 7± 7.96ng/L ,40 .65± 5 .87ng/L ,3 0 .2 6± 3 .61ng/L) ,P均 <0 .0 0 1;死亡组TNF α、IL 1β与IL 6含量 (各为5 5 4.86± 95 .69ng/L ,3 3 8.87± 41.2 1ng/L ,5 97.3 7± 118.3 6ng/L)高于非死亡组TNF α、IL 1β与IL 6含量 ( 2 77.64± 5 4.3 6ng/L ,2 40 .97± 2 0 .87ng/L ,3 84.96± 73 .19ng/L) ,P均 <0 .0 1。结论 :TNF α、IL 1β与IL 6对MODS的病理生理过程可能起作用 ,监测MODS患者血清TNF α、IL 1β与IL 6水平可作为反映病情严重程度和评估预后的一项参考指标     

慢性阻塞性肺疾病患者炎症细胞因子与肺通气功能的相关研究

目的　探讨慢性阻塞性肺疾病 (COPD)患者肺通气功能改变与炎症因子变化之间的关系。方法　稳定期COPD和慢性支气管炎 (简称慢支 )患者各 8例 ,,另有 8名健康者作为对照 ,进行肺功能检查 ,并经支气管肺泡灌洗获取肺泡巨噬细胞进行培养 ,采用酶联免疫吸附 (ELISA)方法测定大肠杆菌内毒素 (LPS)刺激后上清液中白细胞介素 8(IL 8)、IL 1β、IL 6和肿瘤坏死因子α(TNF α)的浓度 ,细胞因子之间相关性采用Pearson相关阵分析 ,肺功能值与细胞因子相关性采用多元后退回归法分析。结果　 (1)肺泡巨噬细胞释放IL 8:加入LPS后COPD组为 [(43± 2 7) μg/L和 (5 7± 41) μg/L],与正常对照组 [(13± 10 ) μg/L和 (2 0± 13 ) μg/L) ]比较差异有显著性 (P <0 .0 5 ) ;与慢支组 [(2 9± 2 1)μg/L和 (3 2± 2 3 ) μg/L]比较差异有显著性 (P >0 .0 5 )。 (2 )加入LPS前、后 ,COPD组、慢支组和正常对照组肺泡巨噬细胞释放IL 1β分别为 [(5 0± 41)ng/L、(94± 5 9)ng/L、(3 7± 3 2 )ng/L、(2 2 5± 10 8)ng/L、(15 3± 175 )ng/L、(70± 3 7)ng/L],与IL 8的释放呈正相关 (P <0 .0 5 ) ;三组肺泡巨噬细胞在LPS刺激后释放TNF α分别为 [(12 3 8± 679)ng/L、(3 0 88± 2 879)ng/L、(13 3 2± 1846)ng/L],与IL 1β呈正相     

不卧床持续性腹膜透析患者血浆和透析排出液中细胞因子的变化及意义

目的 :研究不卧床持续性腹膜透析 (CAPD)患者血浆和腹膜透析排出液中细胞因子的水平与腹膜透析和机体防御功能的关系。　 方法 :用酶免疫法测定 2 1例非感染期CAPD患者血浆和腹膜透析排出液中IL 1α、IL 1β、IL 6、TNFα、IFNγ和可溶性肿瘤坏死因子受体 1(sTNFR1)水平 ,同时做 4h腹膜平衡试验。比较细胞因子水平与腹透情况和腹膜转运特性的关系 ;另外 ,与同期测定的正常人血浆IL 6和sTNFR1水平作对比研究。　 结果 :2 1例CAPD患者血浆和腹透液中各种细胞因子水平分别为 :IL 1α 34 40± 12 87ng/L和 17 6 0± 10 49ng/L(P <0 0 0 1) ;IL 6 8 10± 14 6 9ng/L和 15 7 6 5± 130 2 3ng/L(P <0 0 0 1) ;TNFα 117 30± 195 2 7ng/L和 2 2 90± 13 37ng/L(P <0 0 5 ) ;sTNFR19 76± 0 98μg/L和 1 84± 2 72 μg/L(P <0 0 0 1)。仅在 8例患者血浆及 9例患者腹透液中检测出IL 1β;在 1例患者血浆中测到IFNγ ,腹透液中IFNγ为 2 14± 0 74kU/L。腹透液中IL 6和IFNγ水平呈负相关 (P <0 0 2 )。血浆和腹透液中各种细胞因子水平与腹透时间长短、既往感染与否、透析充分性和超滤量以及腹膜转运特性均无关系。CAPD患者血浆IL 6和sTNFR1水平比正常人明显升高 (P <0 0 0 1)。　 结论 :腹透液中IL     

乌梢蛇水解液对炎性和抗炎性细胞因子的作用

目的　观察乌梢蛇水解液对胶原诱导的关节炎 (CIA)大鼠的炎性细胞因子和抗炎性细胞因子的作用。方法　将CIA大鼠随机分成对照组、低剂量组 (0 .5mg/kg)、中剂量组 (5mg/kg)和高剂量组 (15mg/kg) ,每天给予灌胃乌梢蛇水解液一次 ,共用 2 1d。疗程结束后处死动物分离血清 ,用ELISA方法测定血清中TNF α、IL 1β、IL 4和IL 10的水平。 结果　CIA大鼠外周血清中TNF α水平明显升高而IL 10水平低下 ,IL 1β和IL 4水平与正常大鼠无差异 ,中剂量和高剂量的乌梢蛇水解液能降低CIA大鼠血清TNF α水平和提高血清中IL 10水平 (P <0 .0 5 ) ,对IL 1β和IL 4水平无影响 (P >0 .0 5 )。结论　乌梢蛇水解液能下调CIA大鼠血清中TNF α水平 ,提高IL 10水平     

Graves眼病Th1/Th2相关细胞因子群谱的特征

目的　探讨Graves眼病 (Graves’ophthalmopathy ,GO)发生的免疫机制 ,明确GO的Th1/Th2 相关细胞因子群谱的特征。方法　用逆转录聚合酶链反应 (RT PCR)检测IFN γ、TNF α、IL 2、IL 4、IL 6、IL 10等 6种细胞因子的mRNA转录。结果　与正常对照组相比 ,Graves病恶性突眼组与非突眼组细胞因子的基因转录检出率明显增高 (P <0 .0 1) ;Graves病非突眼组Th2 类细胞因子IL 4和IL 6的基因转录检出率明显高于Th1类细胞因子IFN γ ,TNF α和IL 2的基因转录检出率 (P <0 .0 1) ;而恶性突眼组Th1和Th2 之间细胞因子的基因转录检出率差异无显著性 (P >0 .0 5 )。结论　Graves病恶性突眼者细胞因子的基因转录模式呈典型的Th0 ,细胞免疫和体液免疫共同参与了突眼的发生 ,而非突眼者细胞因子表达向Th2 方向漂移 ,以体液免疫应答为主。     

充血性心力衰竭患者TNF-α和IL-6变化及临床意义

目的 :探讨充血性心力衰竭患者肿瘤坏死因子 (TNF α) ,白细胞介素 6 (IL 6 )的变化及意义。方法 :56例充血性心力衰竭患者和 30例健康体检者为研究对象 ,采用酶联免疫双抗体夹心法测定血清TNF α ,IL 6浓度 ,用二维心脏超声测定左室射血分数 (LVEF)。结果 :1 血清IL 6、TNF α、去甲肾上腺素 (NE)在CHF各组均升高 ,但心功能Ⅱ级组与对照组比较差异不显著 (P >0 0 5) ;心功能Ⅲ级 ,Ⅳ级组IL 6 ,TNF α ,NE明显高于心功能Ⅱ级和对照组 (P均 <0 0 5)。IL 6、TNF α、NE与LVEF呈高度负相关(r=- 0 6 3,P <0 0 1 ;r=- 0 54,P <0 0 5;r=- 0 58,P <0 0 1 )。 2 随心衰程度加重 ,血清TNF α、IL 6和NE浓度越高。TNF α与NE ,IL 6与NE呈明显正相关 (r =0 57,P <0 0 1 ;r =0 51 ,P <0 0 5)。 3 随心衰程度加重 ,血清IL 6与TNF α浓度越高 ,且二者呈正相关 (r =0 39,P <0 0 5)。结论 :CHF患者血清TNF α和IL 6浓度升高 ,尤其中重度CHF患者更加明显 ,并与LVEF呈负相关 ,提示血清IL 6、TNF α水平可作为CHF严重程度的判断与预后指标。     

哮喘患者痰液中炎症介质和细胞因子与气道重塑的关系研究

目的　以支气管粘膜网状基底膜厚度作为气道重塑的指标 ,探讨哮喘患者气道重塑与痰液中细胞因子和炎症介质的关系。方法　对 2 0例哮喘患者和 10名正常对照者经纤维支气管镜行(纤支镜 )支气管粘膜活检 ,测量支气管粘膜网状基底膜厚度 ,用荧光酶联免疫方法测定痰液中的嗜酸细胞阳离子蛋白 (ECP) ,酶联免疫法测定白细胞介素 5 (IL 5 )、肿瘤坏死因子 (TNF α)的水平 ;采用SPSS8 0统计软件作等级相关分析 ,探讨哮喘患者痰液中ECP、IL 5、TNF α水平与支气管粘膜厚度的关系。结果　缓解期哮喘患者支气管粘膜网状基底膜厚度为 (10 1± 2 6 ) μm ,与正常对照组 [(4 4± 1 2 )μm]比较 ,差异有显著性 (P <0 0 0 5 ) ;哮喘组痰液中ECP水平为 (14 4± 80 ) μg/L、IL 5为 (17± 4 ) μg/L、TNF α为 (14 6± 79) μg/L ,与正常对照组 [(81± 4 4 ) μg/L、(14± 4 ) μg/L、(5 3± 36 ) μg/L]比较 ,差异有显著性 (P <0 0 0 5 ) ;两组痰液中ECP、IL 5与支气管粘膜厚度呈明显正相关 (r =0 5 6 9、0 4 6 6 ,P均 <0 0 0 5 ) ;两组痰液中TNF α水平与粘膜厚度无明显相关 (r=0 2 5 4 ,P >0 0 5 )。结论　缓解期哮喘患者支气管粘膜网状基底膜厚度均存在不同程度增厚 ;而痰液ECP和IL 5水平与支气管粘膜厚度呈     

Inhibition of cytokine release from alveolar macrophages in pulmonary sarcoidosis by pentoxifylline: comparison with dexamethasone

STUDY OBJECTIVES: Pentoxifylline (POF) has been shown to suppress the cytokine production from lipopolysaccharide (LPS)-stimulated monocytes/alveolar macrophages (AMs). Sarcoidosis is a granulomatous disease that is driven by the action of tumor necrosis factor (TNF)-alpha and other proinflammatory cytokines. In this study, we aimed to investigate the effects of POF on the production of TNF-alpha, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, and the soluble TNF receptors (sTNFRs) 1 and 2 from AMs in sarcoidosis, and we also compared them with those of dexamethasone (DEX). METHODS: AMs from 14 patients with sarcoidosis were cultured for 24 h with RPMI medium alone or with LPS (100 ng/mL), and with POF at concentrations of 0.01, 0.1, and 1 mmol/L, or with 0.1 mmol/L DEX. Cytokines in the culture supernatants were analyzed by enzyme-linked immunosorbent assay. RESULTS: The results showed that POF induced a dose-dependent suppression of the spontaneous TNF-alpha release from AMs in sarcoidosis (p < 0.001), and that the spontaneous release of the other cytokines was unaffected by POF at all tested concentrations, but a trend for the inhibition of IL-10 production was found (p = 0.092). DEX inhibited the spontaneous release of TNF-alpha (p < 0.001), sTNFR2 (p < 0.05), IL-1 beta (p < 0.05), and IL-10 (p < 0.01). POF also suppressed the LPS-stimulated production of these cytokines except for that of sTNFR1. Similar to POF, DEX inhibited the LPS-stimulated production of these cytokines, but not that of sTNFR1 and IL-1 beta. CONCLUSIONS: Compared with DEX, POF may improve therapeutic regimens in patients with sarcoidosis either by sparing or by replacing corticosteroids. However, the precise clinical value of POF in the treatment of sarcoidosis and other lung diseases will have to be determined in further clinical trials.     

Production of soluble tumor necrosis factor receptors and tumor necrosis factor-alpha by alveolar macrophages in sarcoidosis and extrinsic allergic alveolitis

BACKGROUND: Alveolar macrophage (AM)-derived tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of sarcoidosis and extrinsic allergic alveolitis (EAA). The effects of TNF-alpha are mediated by membrane TNF receptor (mTNFR)-1 and mTNFR-2, and can be blocked by soluble TNF receptor (sTNFR)-1 and sTNFR-2. METHODS: We measured the production of the two sTNFRs and TNF-alpha in AM culture supernatants from 10 patients with active sarcoidosis, 12 patients with EAA, and 9 control subjects using an enzyme-linked immunosorbent assay method. RESULTS: Compared with control subjects, the spontaneous and lipopolysaccharide (LPS)-stimulated production of sTNFR-1, sTNFR-2, and TNF-alpha was significantly increased in patients with sarcoidosis and EAA. The concentrations of both sTNFRs, but especially of sTNFR-2, were closely related to those of TNF-alpha. The LPS-induced increase was 1.5-fold for sTNFR-1, at least fourfold for sTNFR-2, and at least 25-fold for TNF-alpha in all study populations. CONCLUSION: These results indicate that AMs can release the two sTNFRs in relation to TNF-alpha. sTNFR-2 may be more liable to shedding than sTNFR-1. Both sTNFR-1 and sTNFR-2 may be involved in the pathogenesis of sarcoidosis and EAA, possibly as counterregulators of TNF-alpha.     

Thalidomide reduces IL-18, IL-8 and TNF-alpha release from alveolar macrophages in interstitial lung disease.

Thalidomide exhibits diverse actions of anti-inflammation, immunomodulation and anti-angiogenesis. The efficacy of thalidomide treatment in sarcoidosis with lupus pernio is thought to be due to inhibition of tumour necrosis factor (TNF)-alpha. The mechanisms that underlie the properties of thalidomide are still unclear in interstitial lung disease. The current authors investigated the potential inhibitory effects of thalidomide at concentrations of 0.1, 0.01 and 0.001 mM on the production of transforming growth factor-beta, TNF-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, IL-12p40 and IL-18 by alveolar macrophages from bronchoalveolar lavage in patients with sarcoidosis (n = 8), hypersensitivity pneumonitis (HP; n = 8) and idiopathic pulmonary fibrosis (IPF; n = 12). In sarcoidosis and HP patients, thalidomide induced a dose-dependent, partial suppression of lipopolysacchride (LPS)-stimulated TNF-alpha, IL-12p40 and IL-18 release. At the highest thalidomide concentration (0.1 mM), LPS-stimulated IL-8 production was also suppressed. In IPF patients, although spontaneous production of TNF-alpha, IL-12p40, IL-18 and IL-8 was lower than in sarcoidosis and HP patients, with LPS stimulation the cytokines were significantly elevated and also partially inhibited by thalidomide. In conclusion, thalidomide has the potential to improve the therapeutic regimens for sarcoidosis, hypersensitivity pneumonitis and idiopathic pulmonary fibrosis by reducing tumour necrosis factor-alpha, interleukin-12p40, interleukin-18 and interleukin-8 production.     

Increased spontaneous interleukin-10 release from alveolar macrophages in active pulmonary sarcoidosis

The study was designed to determine whether alveolar macrophages (AM) in acute pulmonary sarcoidosis release in vitro the anti-inflammatory cytokine interleukin (IL)-10. To learn more about the coherence between IL-10 and proinflammatory cytokines in active sarcoidosis, the release of interferon (IFN)-gamma, macrophage inhibitory protein (MIP)-1alpha, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was studied and additionally compared to normal controls and patients with pneumonia and interstitial lung fibrosis. AM were obtained by bronchoalveolar lavage from 13 patients with active sarcoidosis, 8 patients with interstitial lung fibrosis, 10 patients with bacterial pneumonia, and 14 normal controls. The spontaneous and stimulated (tumor necrosis factor [TNF]-alpha, IL-1beta) cytokine release was measured in the supernatant of cultured AM by enzyme-linked immunosorbent assay (ELISA). Unstimulated AM from sarcoidosis patients released more IL-10, IFN-gamma, MIP-1alpha, and GM-CSF than normal controls and patients with pneumonia and interstitial lung disease. Stimulation with TNF-alpha or IL-1beta increased the MIP-1alpha and GM-CSF release from AM of normal controls and patients with pneumonia and interstitial lung disease: however, no further enhancement of MIP-1alpha and GM-CSF production was observed in AM from sarcoidosis patients. Exogenous IL-10 reduced the spontaneous and stimulated MIP-1alpha and GM-CSF release in sarcoidosis to a lesser extent than in controls and patients with fibrosis and pneumonia. The up-regulated IL-10 in active pulmonary sarcoidosis may be a compensatory response to the enhanced expression of proinflammatory cytokines in order to down-regulate the inflammatory process. The results suggest an involvement of the anti-inflammatory cytokine IL-10 in the immunopathogenesis of sarcoidosis.     

The differential effect of pentoxifylline on cytokine production by alveolar macrophages and its clinical implications.

The aim of this study was to investigate the effects of pentoxifylline (PTX) on the production of TNF-alpha, IL-1 beta, IL-6 and GM-CSF by lipopolysaccharide (LPS)-stimulated alveolar macrophages (AM). AM and peripheral blood monocytes (PBM) from 10 patients were cultured for 24 h in the presence of LPS (10 micrograms ml-1) and PTX at concentrations of 2.0 mM, 1.0 mM, 0.5 mM, 0.1 mM and 0.01 mM. TNF-alpha and GM-CSF were measured from the culture supernatants of both the AM and PBM from all 10 patients and IL-1 beta and IL-6 from the culture supernatants of the AM from five patients. The TNF-alpha production by AM was significantly suppressed in the presence of PTX at concentrations of 2.0 and 1.0 mM, while production of IL-1 beta, IL-6 and GM-CSF remained unaffected. In PBM cultures, PTX significantly suppressed the production of TNF-alpha and GM-CSF, at all tested concentrations. The present study provides evidence that PTX selectively suppresses the production of TNF-alpha by LPS-stimulated AM and may have a role in the treatment of lung diseases where TNF-alpha is involved. The mode of administration of PTX should take into account the suppressive effect of this drug on GM-CSF production by PBM.     

Interleukin-10 secretion by alveolar macrophages and monocytes in sarcoidosis

BACKGROUND: Alveolitis and the production of proinflammatory cytokines are known features of sarcoidosis. Because of the usually spontaneous resolution of alveolitis despite local secretion of mediators causing inflammation and granuloma formation, we hypothesized that downmodulating mechanisms such as anti-inflammatory cytokines might be involved in this process. OBJECTIVE: Investigation of the secretion of the macrophage deactivating cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) by alveolar macrophages in untreated sarcoidosis of the lung. METHODS: Fourteen consecutive and untreated patients with pulmonary sarcoidosis and 18 volunteers underwent bronchoscopy. Alveolar macrophages (AM) were obtained by bronchoalveolar lavage and the secretion of IL-10 and TGF-beta was studied. RESULTS: Spontaneous IL-10 production by AM was found in 6 of 14 patients and in 2 of 18 controls. The IL-10 level of lipopolysaccharide-stimulated AM was significantly higher in patients. Monocytes secreted significantly more IL-10 than AM, but there was no difference between sarcoid and control monocytes. No difference was found in the secretion of TGF-beta between patients and controls. CONCLUSION: Increased local secretion of IL-10 - but not TGF-beta - may represent a downmodulating mechanism involved in the spontaneous resolution of alveolitis in sarcoidosis.     

Suppressive effects of diesel exhaust particles on cytokine release from human and murine alveolar macrophages

Epidemiological studies have shown an increase in the number of hospital admissions for respiratory diseases in association with high concentrations of particulate matter smaller than 10 micro m (PM(10)). Diesel exhaust particles (DEP) are important components of PM(10). This study was designed to test the effect of DEP on the release of cytokines from alveolar macrophages (AMs). Human and murine AMs were exposed to DEP for 24 hours, and the concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 were measured in the supernatants by enzyme-linked immunosorbent assay (ELISA). DEP (10 micro g/mL) suppressed the spontaneous release of TNF-alpha and IL-6 from murine AMs (P<.05). This suppression was not seen with exposure to carbon particles. Soluble components of DEP had a similar suppressive effect, suggesting that the chemical composition of DEP is responsible for the suppression. Lipopolysaccharide (LPS)- or IFN-gamma-induced TNF-alpha and IL-6 production by murine AMs were suppressed by DEP in a dose-dependent manner (P<.05). DEP also inhibited LPS-stimulated production of TNF-alpha, IL-6, and IL-8 from human AMs (P<.05). Pretreatment of AMs with superoxide dismutase (SOD) (300 IU/mL) prevented the suppressive effect of DEP on AM cytokine production (P<.05). The authors conclude that DEP exposure suppressed the release of cytokines from AMs, and speculate that this suppression could impair normal host defenses.     

Evaluation of bronchoalveolar lavage fluid phospholipids and cytokine release by alveolar macrophages as prognostic markers in sarcoidosis

BACKGROUND: The clinical course of sarcoidosis is unpredictable and reliable laboratory prognostic parameters are lacking. OBJECTIVES: The aim of the present study was to estimate the prognostic value of bronchoalveolar lavage fluid (BALF) phospholipids and cytokine production by alveolar macrophages (AM) in pulmonary sarcoidosis. METHODS: We investigated BALF parameters in 64 subjects (55 patients with sarcoidosis and 9 healthy volunteers as controls). After a period of 12 months, the total sarcoidosis study population was divided into three groups according to radiological, functional and laboratory dynamics: the group with a favorable (n = 15), the one with an unfavorable (n = 16) and the one with an intermediate clinical course of the disease (n = 24). RESULTS: The group of patients with a poor clinical outcome was characterized by a lower percentage of lymphocytes in BALF [20% (4-56%)], rather small amounts of cytokines [TNF-alpha: 1.5 ng/ml/10(6 )(0.08-8.6), IL-6: 5.75 ng/ml/10(6) (1.7-22.5)] and a significant decrease in BALF phospholipids [total lipid phosphorus (TLP): 29.9 micromol/l (13.8-68.3) as compared to 67.5 micromol/l (33.2-127.2) in controls]. Patients with a favorable clinical outcome were shown to have higher lymphocytosis (40%, range 6-64, p < 0.05 versus poor outcome), intensive TNF-alpha and IL-6 release by AM, and close to normal phospholipid content in BALF. CONCLUSIONS: The level of TNF-alpha secretion by AM <3.9 ng/ml/10(6) and total lipid phosphorus in BALF less than 30 micromol/l may serve as markers of poor prognosis in pulmonary sarcoidosis.     

Tumor necrosis factor system in insulin resistance in gestational diabetes

OBJECTIVE: The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy. PATIENTS AND METHODS: Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured. RESULTS: In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01). CONCLUSIONS: Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.