肝炎患者血清IL—2、IFN—γ和IL—10检测的意义

目的：探讨检测IL－2、IFN－γ和IL－10对病毒性肝炎患者的临床意义。方法：利用ELISA法检测97例病毒性肝炎患者血清IL－12、IFN－γ和IL－10水平，动态观察45例接受免疫增强剂治疗的慢性肝炎患者上述细胞因子的变化，结果：急性肝炎患者血清IL－12及IFN－γ水平平均明显升高（P＜0．01）；慢性肝炎、肝硬化患者血清中IL－10明显高于正常对照组（P＜0．01）。免疫增强剂治疗获得完全应答反应的患者治疗期间血清IL－12、IFN－γ水平明显上升（P＜0．01），IL－10水平下降（P＜0．05）。无应答者治疗过程中上述细胞因子无明显变化。结论：Th1型免疫应答对机体清除病毒起关键作用。Th2型免疫应答与感染慢性化及疾病持续发展有关，免疫治疗可使部分Th2型免疫应答占优势的慢性肝炎患者转化为Th1型占优势。     

乙型肝炎患者血清IL-10和IFN-γ水平检测及其意义

目的：检测急、慢性乙型肝炎患者血清IL－10和IFN－γ水平,探讨乙型肝炎慢性化的机理。方法：用双抗夹心ELISA法定量检测25例急性乙肝。35例慢性乙肝和30例正常人血清IL－10和IFN－γ水平。结果：慢性乙肝患者血清IL－10浓度明显高于急性乙肝患者（P＜0．01）,且高于正常对照组（P＜0．01）。而慢性乙肝组患者血清IFN－γ浓度明显低于急性乙肝组（P＜0．01）,两组的血清IFN－γ浓度均明显高于正常对照 组（P＜0．01）。慢性乙肝患者血清IFN－γ浓度与ALT有相关性。结论：慢性乙肝患者IL－10水平增高,限制了IFN－γ合成,削弱了其对HBV清除作用,可能是乙型肝炎慢性化机理之一;慢性乙肝患者血清IFN－γ浓度与ALT有相关性。     

登革病毒感染患者血清IFN—γ和TNF—α的检测及意义

目的：探讨登革病毒感染患者血清INF－γ和TNF－α在登革病毒感染致 病中的作用。方法：应用酶联免疫吸附法（ELISA）测定广州地区30例DV－1感染患者血清IFN－γ和TNF－α的水平。实验数据采用两样本均数t检验法处理。结果：30例登革病毒感染者血清IFN－γ和TNF－α水平比正常健康对照组明显增高（P＜0.05、P＜0.01）。感染病程第一天，患者血清IFN－γ水平开始升高，第二天达高峰，然后逐渐下降。患者血清TNF－α水平第2天明显升高，第3天达高峰，然后逐渐下降。结论：TNF－γ水平开始升高，第二天达高峰，然后逐渐下降。患者血清TNF-α水平第2天明显升高，第3天达高峰，然后逐渐下降。结论：TNF－γ和TNF－α在登革病毒的致病与免疫过程中可能起重要作用。     

肿瘤坏死因子、白细胞介素8、可溶性细胞间粘附分子1和CD11b/CD18在良恶性胸腔积液的价值

目的 研究结核性及恶性胸腔积液患者及血清中肿瘤坏死因子（TNF）、白细胞介素－8（IL－8）、胸液中可溶性细胞间粘附分子1（sICAM-1）及外周血多形核白细胞（PMN）上粘附分子CD11d/CD18在参与胸膜病变的病理生理过程中的作用和在鉴别诊断上的价值。方法 采用放射免疫分析法（RIA法）、双抗体夹心ELISA法及流式细胞仪技术,检测31结核性、31例恶性胸腔积液患者胸液和（或）血清中TNF、IL－8、sICAM－1和CD11d/CD18表达水平,并与31例健康献血者对照。结果 结核性和恶性胸腔积液患者血清中TNF、IL－8含量以及PMN上CD11d/CD18表达显著高于正常对照组（P＜0．01）, 结核性胸液中TNF与IL－8水平和血PMN上CD11d/CD18表达明显高于恶性胸液患者（P＜0．01）,结核性胸粹中sICAM－1水平明显低于恶性胸液（P＜0．01）。胸腔积液中TNF与IL－8、sICAM－1水平呈显著正相关（r＝0．74和r＝0．79,P＜0．01）,血清TNF与PMN上CD11d/CD18的表达呈显著正相关（r＝0．61,P＜0．01）,胸腔积液中sICAM－1水平与血PMN上CD11d/CD18的表达呈显著负相关（经作曲线拟合,Y=1442．31－36．85X∧2＋0．25X∧2,R∧2＝0．59,F＝19．83,P＜0．01）。结论 细胞因子TNF、IL－8和粘附子sICAM－1、CD11b/CD18相互联系,在结核和肿瘤性胸膜病变的免疫 理生理过程中起着重要作用。它们在结核性和肿瘤性胸腔积液患者的表达水平不同,可作为临床上鉴别诊断的参考指标。     

恶性疟原虫保护性抗原复合基因—痘苗病毒重组活疫苗株免疫动物后诱发的Th1细胞免疫反应

目的：测定恶性疟原虫－豆苗病毒重组活疫苗侯选株免疫动物后产生白细胞介素－2（IL－2）和干扰素（IFN）的生活学性水平。方法：用MTT法测定了其诱导的保护性细胞免疫反应（Th1细胞免疫反应）。结果：用重组痘苗病毒在免疫家兔及大白鼠4－6kw后血清中IL－2的生物学活性增强，免疫后6wk家兔，大白鼠及小白鼠3种动物血清中IFN的生物学活性水平比免疫前明显升高。结论：恶性疟原虫－痘苗病毒重组活疫苗候选株免疫动物后可诱发机体产生Th1细胞免疫反应。     

肺结核患者血清前炎细胞因子及其受体的变化

目的 探讨肺结核患者血清TNF－α及受体、IL－1β及受体、IL－6及受体的特征及其临床意义，并明确其在结核病免疫发病中的作用。方法 采用双抗体夹心ABC－ELISA法检测41例活动性肺结核患者、21例非活动性肺结核患者和20名正常人血清TNF－α、sTNF-RⅠ、IL－1β、IL－1R、IL－6、IL－6R的水平，同时对17例活动性肺结核患者抗结核治疗后上述CK水平进行了随访。结果 活动性肺结核组和非活动性肺结核组血清TNF－α、sTNF-RⅠ、IL－1β、IL－1R、IL－6、IL－6R水平及TNF－α/sTNF-RⅠ比值均显著高于正常对照组（P＜0.01-0.05)。活动性肺结核组血清TNF-α、sTNF-RⅠ、IL－1β、IL－1R、IL－6、IL－6R水平及TNF－α／sTNF-RⅠ比值显著高于非活动性肺结核组（P＜0.01-0.05)。空洞组血清TNF－α、sTNF-RⅠ、IL－1β、IL-6水平及TNF－α/sTNF-RⅠ比值低于无空洞组（P＜0.01-0.05)。抗结核治疗2月末，17例患者中有15例患者血清TNF－α、sTNF-RⅠ、IL－1β、IL－1R、IL－6、IL－6R水平及TNF－α／sTNF-RⅠ比值均较治疗前明显降低（P＜0.01-0.05)，且上述患者临床症状改善，痰菌阴转，胸片病灶吸收好转、空洞缩小或闭合。但有2例患者血清上述CK水平较治疗前未明显降低，痰菌未阴转。结论 TNF－α、sTNF-R、IL－1β、IL-1R、IL－6、IL－6R等均参与结核病免疫发病过程。肺结核患者血清前炎细胞因子及受体水平的检测有助于了解疾病的活动性，判断病情及预后，监测抗结核治疗的效果。     

系统性红斑狼疮和乙型肝炎病毒感染的相互关系及细胞因子的调节作用

目的 研究系统性红斑狼疮（SLE）与乙型肝炎病毒（HBV）感染的相关性及Th1/Th2型细胞因子的调节作用。方法 运用酶联免疫吸附试验（ELISA）法检测131例SLE患者及582名年龄性别相对应健康体检者人群HBV标志物，并进行发组检测各组中干扰素IFN－γ、白细胞介素－10（IL－10）的血清含量。结果 131例SLE患者HBsAg均阴性，较对照组（7．7％）明显降低，HBeAb、HBcAb伴有HBsAb阳笥者为43．8％，较对照组（26．1％）明显增同。SLE患者血清中IFN－γ的含量低于对照组。SLE合并HBV感染组IFN－γ的含量比SLE组明显增高，与正常对照组比较差异无显著性。SLE患者IL－10比对照组明显增高，但SLE合并HBV感染组与慢性HBV感染组相比IL－10量差异无显著性。结论 在SLE中乙型肝炎表面标志物HBsAg明显降低，SLE感染HBV后更易产生HBsAb，表明SLE发病与HBV感染并无相关。SLE合并HBV感染者中IL－10、IFN－γ与SLE病人有明显差异，向HBV感染者偏移。此现象可能与Th1/Th2型细胞因子在疾病中相互调节、相互制约有关。     

慢性乙型肝炎患者血清IL018、IFN0γ的检测及临床意义

目的:探讨慢性乙型肝炎(CHB)患者血清IL18、IFNγ水平的变化及其临床意义。方法:应用ELISA法检测49例CHB患者血清IL18、IFNγ水平,并同时检测肝功能和乙肝病毒标志物。结果:CHB患者血清IL18、IFNγ水平均显著高于对照组(P<0.001),其升高水平依次为重度>中度>轻度,以CHB重度增高最为显著;血清IL18、IFNγ水平与血清ALT、TBil呈正相关(P<0.01或P<0.05);HBeAg阴性组血清中IL18水平较HBeAg阳性组明显升高(P<0.001),而IFNγ则无明显变化。结论:血清IL18、IFNγ参与了CHB的病理生理过程,并且与肝炎的病情变化密切相关,检测血清IL18、IFNγ水平有助于了解肝组织炎症活动及肝细胞损伤程度。同时,IL18在抗病毒方面发挥着重要作用。     

6种细胞因子对巨细胞病毒感染人胚肺成纤维细胞的影响

目的 研究6种细胞因子（IL－1β、IFN－α、IFN－γ、GM－CSF、TGF－β1、bFGF）对人巨细胞病毒（HCMV）感染人胚肺成纤维细胞（HEL）的影响,探讨细胞因子在HCMV感染免疫中的作用。方法 用不同浓度的6种细胞因子分别作用于HEL,24h后感染病毒,研究6种细胞因子对HCMV感染HEL的影响。结果 在病毒感染前,IL－1β、IFN－α、INF－γ、bFGF作用于HEL可抑制HCMV的增殖;TGF－β1作用于HEL可增加HCMV的增殖,上述细胞因子对病毒复制的影响与细胞因子的浓度有关。GM－CSF地人巨细胞病毒感染人胚肺成纤维细胞无明显影响。结论 细胞因子在HCMV感染免疫过程中起重要作用。     

系统性红斑狼疮患者外周血单个核细胞分泌白细胞介素-10 干扰素-γ水平的研究

目的：通过检测系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）分泌细胞因子白细胞介素－10（IL－10）、干扰素－γ（IFN－γ）水平，探讨了T淋巴细胞亚群与SLE发病关系。方法：采用酶联免疫吸附法（ELISA）测定30例SLE患者和10名健康志愿者PBMC培养上清IL－10和IFN－γ水平。结论：①SLE活动组PBMC自发分泌IL－10水平明显升高，与非活动组、对照组比较差异有显著性（P＜0．001）；非活动组明显高于对照组（P＜0．01）。②PBMC分泌IFN－γ水平三组（SLE活动组、非活动组和对照组）比较差异无显著性（P＞0．05）。结论：IL－10、IFN－γ作为区分CD4T细胞亚群的指标之一，间接反映了Th1、Th2细胞活化状态。本文研究结果显示，SLE患者PBMC分泌IL－10水平明显增高，且增高程度与病情活动性相关，IFN－γ分泌水平无明显变化。提出Th2型细胞因子介导的免疫应答在SLE的发病机制中占主导地位，即“Th2优势应答”。我们认为PBMC分泌IL－10水平对SLE诊断和病情活动性监测均有一定临床意义。寻找有效方法调节SLE患者体内IL－10水平，从而调节Th1/Th2平衡，将为治疗SLE开辟一条新途径。     

Increased levels of circulating interleukin-18 in patients with advanced tuberculosis

Interleukin-18 (IL-18) has recently been identified as an interferon- gamma-inducing factor and it plays an important role in the Th1 response. We measured serum levels of IL-18 and interferon-gamma (IFN-gamma) in 43 patients with pulmonary tuberculosis and 25 healthy control subjects. Significantly increased levels of circulating IL-18 and IFN-gamma were found in pulmonary tuberculosis as compared with those in healthy control subjects. Circulating IL-18 and IFN-gamma correlated with the extent of disease in pulmonary tuberculosis. We found significantly increased levels of circulating IL-18 and IFN-gamma in the patients with high-grade fever. Circulating IL-18 significantly correlated with circulating IFN-gamma. IL-18 may play an important role in immune response to human infection with Mycobacterium tuberculosis.     

Significance of the frequency of CD4+CD25+CD127- T-cells in patients with pulmonary tuberculosis and diabetes mellitus

Background and objective: Pulmonary tuberculosis and diabetes mellitus (DM) are closely associated. The objective of this study was to determine whether the expression of CD4+CD25+CD127? T‐cells (regulatory T‐cells (Treg)) is associated with diabetic pulmonary tuberculosis. Methods: Flow cytometry was used to determine the frequencies of CD4+CD25+ and CD4+CD25+CD127? T‐cells in peripheral blood, bronchoalveolar lavage fluid (BALF) and pleural effusions from 120 patients (30 with pulmonary tuberculosis and DM (TBDM), 30 with pulmonary tuberculosis without DM (TB), 30 with tuberculous pleurisy without DM (TBP) and 30 healthy volunteers). The concentrations of interferon (IFN)‐γ and interleukin (IL)‐10 in BALF and pleural effusions were determined by enzyme‐linked immunosorbent assay. Results: Treg frequencies in peripheral blood were significantly higher in patients with TBDM, TB and TBP than in the control group, with the frequency in TBDM being the highest (P < 0.01 for all). In TBP patients, Treg frequencies were significantly lower in pleural effusions than in peripheral blood. In TB patients, Treg frequencies in BALF and peripheral blood were not significantly different. However, in TBDM patients, Treg frequencies were significantly higher in BALF than in peripheral blood. IL‐10 expression was significantly higher, and IFN‐γ expression was significantly lower in BALF of TBDM patients compared with BALF and pleural effusions of TB patients. Conclusions: In patients with pulmonary tuberculosis and DM, the imbalance between Treg and effector T‐cells at pathological sites may be associated with weakened immunity and clinical manifestations of TB.     

The value of serum interferon-gamma level in the differential diagnosis of active and inactive pulmonary tuberculosis

Interferon (IFN)-gamma plays a pivotal role in protective immunity against Mycobacterium tuberculosis. Elevations of IFN-gamma have been found in the affected lung and bloodstream of patients with pulmonary tuberculosis. In the present study, we aimed to investigate the role of serum IFN-gamma level in the differential diagnosis of active and inactive pulmonary tuberculosis. Fourty seven patients with newly diagnosed active pulmonary tuberculosis, 21 patients with inactive pulmonary tuberculosis, and 20 healthy volunteers were enrolled in the study. Serum samples were collected from each subject and stored at - 70 degrees C until the analysis of IFN-gamma. The mean value of IFN-gamma levels were 9.3 +/- 4.6 pg/mL in patients with newly diagnosed pulmonary tuberculosis, 9.8 +/- 3.8 pg/mL in patients with inactive tuberculosis, and 10.2 +/- 3.4 pg/mL in healthy controls. The comparison of IFN-gamma levels of the three groups was not found statistically significant (p= 0.4). Serum IFN-gamma level was not found to be valuable in the differential diagnosis of active and inactive pulmonary tuberculosis.     

肺癌Th1/Th2免疫反应状态的研究

为探讨肺癌细胞及肺癌患者外周血单个核细胞Ｔｈ１／Ｔｈ２的免疫反应状态,为肿瘤的免疫治疗提供依据,以ＩＬ－２和ＩＦＮ－ｒ代表Ｔｈ１型细胞因子,ＩＬ－４、ＩＬ－６和ＩＬ－１０代表Ｔｈ２型细胞因子,用ＲＴ－ＰＣＲ方法检测了三种人肺癌细胞株及２３例肺癌细胞患者ＰＢＭＣ中Ｔｈ１／Ｔｈ２型细胞因子ｍ－ＲＮＡ的表达。结果显示,三种肺癌细胞的Ｔｈ１型因子ＩＦＮ－ｒ和ＩＬ－２均无表达,而Ｔｈ２型因了ＩＬ－４、ＩＬ－     

Role of interleukin-18 and T-helper type 1 cytokines in the development of Mycoplasma pneumoniae pneumonia in adults

STUDY OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine, originally termed interferon (IFN)-gamma-inducing factor, which promotes T-helper type 1 (Th1) cytokine responses. We recently reported that serum IL-18 levels were elevated in children with Mycoplasma pneumoniae pneumonia (MP). In this study, we investigated the contribution of IL-18 to the infection and assessed the Th1 cytokine response to pulmonary involvement in adults. METHODS: We investigated the clinical course, pulmonary involvement, and serum levels of IL-18, IFN-gamma, IL-12p40, and soluble IL-2 receptor (sIL-2R) in 21 patients with acute-stage MP and in 21 age- and sex-matched control subjects. RESULTS: Significantly (p < 0.001) increased serum IL-18 (median, 248 pg/mL [range, 89 to 441 pg/mL] vs. median, 126 pg/mL [range, 47 to 217 pg/mL]) and sIL-2R (median, 617 U/mL [range, 410 to 1,032 U/mL] vs. median, 425 U/mL [range, 268 to 601 U/mL]) were found in patients with MP as compared with healthy control subjects, and there was a tendency toward increased serum IFN-gamma and IL-12p40. Circulating IL-18 values had a positive correlation with serum sIL-2R levels (r = 0.62, p = 0.028) and the number of affected pulmonary lobes (sigma = 0.61, p = 0.024), but not with the serum levels of antibodies to M pneumoniae, IFN-gamma, or IL-12p40. Serum IL-18 and sIL-2R values in severe cases were significantly higher (p < 0.03) than those in mild cases. IFN-gamma and sIL-2R levels in four patients with pleural effusion were significantly (p < 0.05) higher than those in the other 17 subjects. CONCLUSIONS: Serum levels of IL-18 were raised during the acute phase of MP. We suggest IL-18 and Th1 cytokines may play a significant role in the immunopathologic responses in MP.     

正规抗结核治疗对初治肺结核患者血清中血管活性肠肽水平的影响

目的 探讨正规抗结核治疗对初治肺结核患者血清中血管活性肠肽水平的影响及其与Th1型细胞因子γ-干扰素和Th2型细胞因子白细胞介素(IL)-4的相关性.方法 选择45例初治肺结核患者,其中30例Ⅲ型肺结核患者进行正规治疗2个月,观察血管活性肠肽、白细胞介素-4、γ-干扰素的变化情况,并与15例Ⅱ型肺结核患者及健康对照组相比较.结果 肺结核组血清VIP和IL-4水平均高于对照组,γ-干扰素水平低于对照组,Ⅲ型肺结核患者抗结核治疗2个月后,血清VIP和IL-4均明显低于治疗前,γ-干扰素水平明显低于对照组.结论 正规抗结核治疗2个月后,肺结核患者血清VIP水平明显下降,提示VIP对评价抗结核疗效具有一定的参考意义.     

Interferon gamma/IL10 ratio defines the disease severity in pulmonary and extra pulmonary tuberculosis

Several cytokines (IFN gamma, TNF alpha, IL10 and IL6) show an association with either disease localization or dissemination in tuberculosis. There are also reports of involvement of extra-pulmonary sites in tuberculosis with differential clinical severity. However, no comparative study of biomarkers across the disease severity spectrum is available. This was the purpose of the current study. Cytokines (IFN gamma, TNFalpha, IL10 and IL6) secreted in response to a panel of stimulants (PHA, LPS or mycobacterial antigens) in whole blood were determined in eighty-two tuberculosis patients. WHO criteria was applied for stratification of patients according to disease severity: disseminated and or severe disease (EPTB1; N=29); disease localized to lung parenchyma (PTB; N=32) and disease localized to peripheral sites without lung involvement (EPTB2; N=21). Mycobacterial antigens induced IFN gamma/IL10 ratio showed a direct relationship with disease severity ranking (median ratios: EPTB1=0.21; PTB=0.85; EPTB2=7.7) and the highest correlation (Spearman Rank; rho=0.673, p<0.000001). IFN gamma/IL10 ratio also rank ordered clinical severity as it relates to anatomic sites. IFN gamma/IL10 ratio may therefore provide a useful objective marker of disease severity in both pulmonary and extra-pulmonary tuberculosis.     

Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy

Immunological and clinical profiles were evaluated in 2 groups: human immunodeficiency virus (HIV)-uninfected and HIV-infected patients, with newly diagnosed pulmonary tuberculosis (TB), and tuberculin-skin-test-reactive healthy control subjects. HIV-uninfected patients with TB were also followed up longitudinally during and after chemotherapy. At the time of diagnosis, purified protein derivative (PPD)-stimulated production of interferon (IFN)-gamma by peripheral blood mononuclear cells from TB patients was depressed, compared with that of healthy control subjects, whereas levels of transforming growth factor (TGF)-beta and interleukin (IL)-10 were increased. In longitudinal studies, PPD stimulated production of IL-10 and TGF-beta returned to baseline by 3 months, whereas IFN-gamma production remained depressed for at least 12 months. These data indicate that the immunosuppression of TB is not only immediate and apparently dependent (at least in part) on immunosuppressive cytokines early during the course of Mycobacterium TB infection but is also long lasting, presumably relating to a primary abnormality in T-cell function.