Serum tumour necrosis factor-alpha,interleukin-2 and interleukin-10 activation in stable angina and acute coronary syndromes

BACKGROUND: Dynamic instability of coronary atherosclerotic plaque results in the development of both unstable angina and myocardial infarction. The aim of the study was to investigate the dynamics of serum concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-10, and IL-2 in patients with myocardial infarction (MI) and unstable angina (UA) as compared to stable angina (SA) patients and healthy volunteers. METHODS: A total of 189 patients with coronary artery disease (CAD) were studied: 100 patients with SA (class II/III according to CCS), 57 patients with UA (Braunwald class IIIB; determinations at 6, 24, and 48 h after chest pain), and 32 patients with MI (determinations at admission, on the 7th and 30th days after MI). Twenty healthy volunteers acted as controls. RESULTS: Serum TNFalpha levels were elevated in all CAD groups (SA: 17.3+/-4; UA: 18.7+/-4; MI: 22.0+/-3 pg/ml; p<0.001) in comparison to the controls (8.3+/-1.4 pg/ml). However, the highest values were characteristic of MI patients, especially values obtained at admission (p<0.01 versus SA and UA). Mean serum concentrations of IL-2 were significantly higher in patients with MI and UA (89.6+/-40; 87.0+/-24 pg/ml, respectively; p<0.01) when compared to SA and the control group (58.3+/-49; and 51.5+/-39, respectively). Serum IL-10 levels were also higher in MI and UA patients. Levels of IL-2 and IL-10 measured following chest pain in unstable patients, as well as their consecutive determinations in MI patients did not show any change dynamics, that is, they were persistently elevated. CONCLUSIONS: When compared to stable CAD and healthy subjects, acute coronary syndromes are associated with long-term increase of serum concentrations of pro- and anti-inflammatory cytokines. It seems likely that sudden CAD progression leading to acute coronary syndromes is triggered/accompanied by prolonged immune activation.     

免疫治疗对支气管哮喘小鼠树突细胞共刺激分子的影响

目的应用卵白蛋白(OVA)建立特异性免疫治疗小鼠模型,探讨特异性免疫治疗对支气管哮喘(简称哮喘)小鼠树突细胞(DC)表面分子CD80、CD86表达的影响。方法120只BALB/c小鼠按随机数字表法分为哮喘模型组(A组)40只:用0.1%OVA 10μg连续腹腔注射(共70μg)及1%OVA雾化吸入(共300 mg);免疫治疗模型组(B组)40只:用与A组同剂量的OVA致敏和激发,同时连续尾根部皮下注射OVA 1 mg;对照组(C组)40只:以磷酸盐缓冲液代替OVA,其余同A组。留取各组肺组织切片,经苏木精-伊红(HE)染色观察炎症反应;用酶联免疫吸附测定(ELISA)法检测血清OVA特异性免疫球蛋白IgE(sIgE)及脾脏T淋巴细胞中白细胞介素2(IL-2)和IL-4的分泌。分离各组小鼠脾脏DC,用流式细胞仪检测其表面CD80、CD86分子表达。分离正常小鼠脾脏T淋巴细胞,与上述各组DC共培养;用ELISA法检测T淋巴细胞IL-4、IL-5的分泌量;用3H-胸腺嘧啶核苷(3H-TdR)掺入法检测其增殖反应。结果(1)B组小鼠肺组织中支气管及血管周围以大量淋巴细胞和嗜酸粒细胞为主的炎性细胞浸润明显轻于A组,但并未完全消失;A组血清sIgE吸光度(A)值为712±129,B组为124±59,C组为20±13,A、C组间比较差异有统计学意义(P<0.05),B、C组比较差异无统计学意义(P>0.05)。B组T淋巴细胞分泌IL-2、IL-4水平分别为(8±3)、(8.4±4.3)pg/m l,A组分别为(22±8)、(32.4±12.1)pg/m l,C组分别为(6±4)、(5.1±1.1)pg/m l,A、B两组比较差异有统计学意义(P<0.05),B、C组间比较差异无统计学意义(P>0.05);(2)B组DC表面CD86、CD80阳性表达率分别为58.23%、95.63%,A组分别为77.59%、96.98%,C组分别为77.37%、77.84%;(3)与B组DC共培养的正常小鼠T淋巴细胞体外经OVA刺激后,IL-4、IL-5水平分别为(10.8±2.3)、(18.8±3.8)pg/m l,A组分别为(17.3±4.7)、(35.7±7.9)pg/m l,C组分别为(5.7±2.7)、(11.0±2.2)pg/m l,A、B两组比较差异有统计学意义(P<0.05),B、C组间比较差异无统计学意义(P>0.05);B组DC与正常小鼠T淋巴细胞共培养时,刺激指数(SI)为3.8±0.7,A组为11.5±3.2,C组为5.8±1.5,A、B组间比较差异有统计学意义(P<0.05);B、C组间比较差异无统计学意义(P>0.05)。结论建立了OVA特异性免疫治疗小鼠模型;DC表面CD86分子表达的下调可能是OVA特异性免疫治疗诱导T淋巴细胞功能丧失的机制之一。     

Serial circulating concentrations of C-reactive protein, interleukin (IL)-4, and IL-6 in patients with acute left heart decompensation

BACKGROUND: Interleukin (IL)-6 has recently been shown to have negative inotropic effects, and several studies have reported increases in circulating concentrations of this cytokine in patients with depressed left ventricular ejection fraction and chronic left heart failure. However, most previous clinical studies have measured cytokines in compensated chronic heart failure. HYPOTHESIS: The purpose of this study was to examine the temporal evolution of circulating concentrations of C-reactive protein (CRP) and cytokines in patients with cardiomyopathy and acute cardiac decompensation, free of infection and unstable angina. METHODS: The time course of circulating concentrations of CRP, an anti-inflammatory cytokine interleukin (IL)-4, and a proinflammatory cytokine IL-6 were studied in eight patients with cardiomyopathy and acute cardiac decompensation in the absence of infection or unstable angina. Control samples were obtained from eight age-matched asymptomatic subjects. RESULTS: Increased circulating concentrations of CRP (2.6 +/- 0.8 mg/dl), IL-4 (164.6 + 36.5 pg/ml), and IL-6 (17.1 +/- 5.1 pg/ml) were found in all eight patients during acute cardiac decompensation; these values decreased significantly with the resolution of symptoms of cardiac decompensation (0.5 +/- 0.1 mg/dl, 77.8 +/- 23.6 pg/ml, 2.3 +/- 0.1 pg/ml, respectively, p < 0.05 for both). There was a significant correlation between peak CRP and peak IL-6 (p < 0.05). CONCLUSIONS: In patients with acute left heart decompensation in the absence of infection or coronary events, CRP, IL-4, and IL-6 increased and returned toward normal levels as the symptoms of heart failure resolved. Since the changes in concentrations of CRP, IL-4, and IL-6 in patients with heart failure are dynamic, the distinction between compensated and decompensated state is important when discussing the significance of acute reactive proteins or cytokines in the pathogenesis of heart failure.     

The selected pro- and anti-inflammatory cytokines in the patients with coronary heart disease: preliminary communication

Recent findings suggest that inflammation and cytokines regulation may play a role in the pathogenesis of atherosclerosis and coronary heart disease. The aim of this study was to assess serum concentrations of selected pro- (TNF alpha) and antiinflammatory (IL-10) cytokines in patients with coronary heart disease. We studied 29 patients with coronary heart disease: 14 with stable angina (group I) and 15 with unstable angina (group II). The control group (group K) consisted of 10 healthy subjects. Patients with inflammatory diseases, previous myocardial infarction (last 6 months) and with ECG abnormalities, that would invalidate ST-segment analysis, were excluded from examined groups. We evaluated: clinical state of patients and results of some diagnostic examinations (lipids, ECG, echocardiography, coronary angiography, concomitant diseases). In each patients serum levels of TNF alpha and IL-10 were measured according to the special protocol by ELISA. The mean serum concentrations of TNF alpha and IL-10 were significantly higher in group I (respectively: 18.75 +/- 11.7 pg/ml, 89.0 +/- 114.9 pg/ml) and II (14.21 +/- 5.9 pg/ml, 49.38 +/- 72.9 pg/ml) in comparison to the healthy subjects (9.41 +/- 1.7 pg/ml, 9.69 +/- 4.5 pg/ml). We found positive correlations between mean TNF alpha and IL-10 concentrations in group II (48 hours after last symptom) and between mean TNF alpha concentration and LVM (left ventricular mass), LVMI (left ventricular mass index) in group I. The concentrations of TNF alpha and IL-10 did not correlate with other clinical parameters. The results of our study suggest that serum concentrations of pro- (TNF alpha) and antiinflammatory (IL-10) cytokines may be increased in patients with stable and unstable angina. These increased concentrations do not reflect the clinical state of patients.     

Expression of activation antigens on lymphocyte surface and circulating platelet-leukocyte aggregates in ischaemic heart disease

BACKGROUND: Data from literature documented the role of the activation of circulating T lymphocytes and increased leukocyte adhesion to blood platelets in the destabilisation of an atheromatous plaque and progression of ischaemic heart disease to acute coronary syndrome. AIM: To assess whether there is an increased proportion of activated T lymphocytes and platelet-leukocyte aggregates (PLA) in the circulating blood in patients with myocardial infarction or with stable angina, and to examine whether these changes are related to the progression of clinical symptoms or coronary angiography results. METHODS: The study group consisted of 36 patients with ST-segment elevation acute myocardial infarction (STEMI), confirmed by elevated troponin T level (36 patients, 26 males, 10 females, mean age 61.8 years, range 42-78 years), 30 patients with stable angina and single-vessel disease (24 males, 6 females, mean age 58.8 years, range 43-69 years), and 20 control healthy age and gender-matched subjects. Lymphocyte activation was evaluated by the assessment of T lymphocytes CD3+ /CD69+, CD3+/HLA-DR+ and CD4+/CD154+. The PLA assessment, including platelet-granulocyte aggregates (PGA), platelet-monocyte aggregates (PMA) and platelet-lymphocyte aggregates (PlymphA) was based on the measurement of the proportion of CD45+/CD41a+ cells with the use of flow cytometry. RESULTS: The proportion of T lymphocytes CD3+/HLA-DR+, CD3+/CD69+ and CD4+/CD154 was significantly higher in patients with STEMI than in controls, and T lymphocytes CD3+/CD69+ - significantly higher in STEMI group than in both patients with angina or controls. There was no significant relationship between the proportion of activated lymphocytes and duration of anginal pain, troponin T concentration or the number of coronary vessels with critical stenosis. The proportion of PGA, PMA and PlymphA was significantly greater in STEMI patients than in patients with angina or controls. There was a significant positive correlation between the proportion of PLA and PMA, and the duration of anginal pain. Patients with stable angina had a significantly higher proportion of T lymphocytes CD3+/HLA-DR+ compared with controls. CONCLUSIONS: Circulating T lymphocyte activation is present in ischaemic heart disease. This phenomenon is more pronounced in patients with acute MI than in those with stable angina, and is not related to the degree of cardiac injury. An increased formation of platelet-leukocyte aggregates is also present in patients with acute MI.     

Evaluation of CD30 as a marker for th2 lymphocytes in bronchoalveolar lavage in interstitial lung diseases

Several studies have been carried out to clarify the relationship between CD30 expression and Th2 lymphocytes, although the results have been controversial. To investigate whether CD30 is a useful marker for Th2 lymphocytes in bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD), we studied six control subjects and 31 patients with ILD (12 with idiopathic pulmonary fibrosis, seven with hypersensitivity pneumonitis, three with chronic eosinophilic pneumonia and nine with sarcoidosis). The levels of interleukin-5 (IL-5) (secreted by Th2 cells), interferon-gamma (IFNgamma) (secreted by Th1 cells) and the expression of CD30 on lymphocytes were determined in BAL fluid. There were no differences in the percentage of CD30+ lymphocytes between controls and patients with ILD (0.8+0.4% vs. 2+/-0.4%). In order to determine the relationship between Th2 cells and CD30 expression, we divided the patients into two groups according to BAL IL-5 levels. Group I consisted of eight patients (three chronic eosinophilic pneumonia, three hypersensitivity pneumonitis, two idiopathic pulmonary fibrosis) with high IL-5 levels (298+/-138 pg ml(-1)). Group II consisted of the remaining 23 ILD patients with normal IL-5 levels (0.9+/-0.6 pg ml(-1)). The percentage of eosinophils in BAL fluid was significantly higher in group I compared with group 11 (34+/-16% vs. 3+/-1%, P < 0.05). A correlation between CD30+ lymphocytes and IL-5 in group 1 was not shown. There were no differences in the number of CD30+ I we found a significant correlation between IL-5 levels and the percentage of eosinophils (r = 0.95, P < 0.0001). Our results suggest that CD30 does not appear to be a useful marker for Th2 lymphocytes in BAL from patients with ILD.     

Plasma noradrenaline as an index of sympathetic tone in coronary arterial disease: the confounding influence of clearance of noradrenaline

Kinetics of [3H]noradrenaline in the plasma were compared with plasma noradrenaline concentration in assessing overall sympathetic activity in six groups totalling 118 subjects. Arterial plasma noradrenaline in 21 control subjects was 204 +/- 14 pg/ml, similar to 20 patients with stable angina not treated with beta-blockers (194 +/- 25 pg/ml) and to 31 patients with stable angina treated with beta-blockers (232 +/- 19 pg/ml). Plasma noradrenaline was increased in 17 patients with unstable angina (366 +/- 50 pg/ml, P less than 0.01), in 14 patients with recent acute myocardial infarction (460 +/- 44 pg/ml, P less than 0.001) and in 15 patients with treated cardiac failure (582 +/- 78 pg/ml, P less than 0.001). Whole body clearance of noradrenaline from plasma was, however, reduced in each of the last three groups compared to controls by 20% (P less than 0.05), by 34% (P less than 0.01) and by 31% (P less than 0.01), respectively. In the 31 patients with stable angina on beta-blockers, clearance of noradrenaline was also reduced by 20% (P less than 0.05). Whole body noradrenaline spillover, a potentially more accurate measure of overall sympathetic activity than concentration of noradrenaline in plasma, was 235 +/- 20 ng min-1 m-2 in controls, was similar in subjects with stable angina (no beta-blockers; 260 +/- 34 ng min-1 m-2, beta-blockers; 200 +/- 17 ng min-1 m-2), but was increased in patients with unstable angina (310 +/- 27 ng min-1 m-2, P less than 0.05), with recent acute myocardial infarction (346 +/- 40 ng min-1 m-2, P less than 0.05) or with heart failure (438 +/- 65 ng min-1 m-2, P less than 0.01). Overall sympathetic activity is unchanged in stable angina, but is progressively increased in patients with unstable angina, recent myocardial infarction or heart failure. Plasma concentration of noradrenaline fails accurately to reflect this as a result of decreased clearance of noradrenaline in these patients. The results show the potential limitations of measurement of noradrenaline in the plasma as an index of overall sympathetic activity and the importance of assessing clearance.     

Inflammatory cytokine release in patients with unstable angina after coronary angioplasty

The aim of the present study was to investigate inflammatory cytokine release and the interaction with platelets in patients with unstable angina (UA) after coronary angioplasty. In 50 patients with stable angina (SA) and 58 patients with UA, serial venous blood samples were obtained immediately before, and 30 minutes, 4, 12, 24, 48 and 72 hours, and 7 days after coronary angioplasty. Plasma concentrations of IL-8 and vWF were determined by immunoassay, while the expression of CD11 b/CD18 on monocytes and the expression of CD41 on platelets were assessed by flow cytometry. Differences in the baseline plasma concentrations of IL-8, vWF and CD11b/CD18, CD41 were found in the UA and SA groups before angioplasty (101.1 +/- 31.28 pg/mL to 55.8 +/- 17.24 pg/mL, 137.67 +/- 38.14% to 107.40 +/- 28.67% and 318.67 +/- 36.85 MFI to 240.72 +/- 28.43 MFI, 147.5 +/- 23.18 MFI to 104.43 +/- 26.68 MFI all p < 0.05). The peak plasma levels of IL-8 (172.24 +/- 37.82 pg/mL at 12 hours) and vWF (256 +/- 42.32% at 4 hours) significantly increased after coronary angioplasty (both p < 0.01), and were associated with significant time course increases in surface expression of CD11b/CD18 (p < 0.01) and CD41 (p < 0.01). The levels of plasma IL-8 and vWF were significantly higher pre- and post-procedure in UA patients with lesion type C compared to types A or B (p < 0.05), but there were no differences for pre-procedure in the SA group patients with different lesion types (p > 0.05). There were significant correlations between plasma IL-8 and monocyte CD11b/CD18, vWF and CD41 in the UA group (r = 0.5248, r = 0.6240 both p < 0.01, respectively). The findings demonstrate increases in plasma IL-8 and CD11b/CD18 as inflammatory mediators, vWF and CD41 as the abnormal coagulation activity may therefore yield a rationale for pharmacological anticytokines in patients with UA after coronary angioplasty.     

Effect of carni Q-gel (ubiquinol and carnitine) on cytokines in patients with heart failure in the Tishcon study

INTRODUCTION: There is evidence that both carnitine and coenzyme Q 10 (Co Q), which are important for the functioning of myocardial mitochondria, are deficient in patients with congestive heart failure, in association with increased pro-inflammatory cytokines. It is possible that supplementation with ubiquinol and L-carnitine may protect these patients by decreasing inflammation. SUBJECTS AND METHODS: In a randomized, double-blind, placebo-controlled trial, the effects of carni Q-gel (2250 mg/d L-carnitine and 270 mg/d hydrosoluble ubiquinol) were examined for 12 weeks. Thirty-one patients with heart failure received intervention (group A) and another 31 patients served as controls (group B). Serum levels of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha and IL-10 could be studied among 29 patients in each group. Statistical analysis was conducted by analysis of variance and chi square test. RESULTS: Echocardiographic ejection fractions were lower at baseline (38.8 + 7.6 vs. 39.3 + 6.7% in the intervention and control groups, respectively) among both group of patients, indicating class II-IV heart failure. Serum concentration of interleukin-6 (IL-6), a pro-inflammatory cytokine, was high (18.7 +/- 5.8 vs. 15.0 +/- 3.3 pg/ml, normal 0.0-3.9) and IL-10 (anti-inflammatory) was normal (3.4 +/- 1.5 vs. 2.9 +/- 1.0 pg/ml, the normal range is 1.5-3.1 pg/ml) in both groups at baseline. After 12 weeks, there was a marked reduction in IL-6 in the intervention group without such changes in the control group (7.6 +/- 1.5 vs. 11.4 +/- 2.5 pg/ml, P < 0.01. IL-10 showed only the non-significant decrease in both groups from the baseline levels (3.2 +/- 1.0 vs. 2.8 +/- 0.9 pg/ml). TNF-alpha, which was comparable at baseline (17.6 +/- 4.3 vs. 20.0 +/- 5.3 pg/ml), also showed a greater decline in the carni Q-gel group compared to the placebo group (12.5 +/- 3.3 vs. 17.2 +/- 3.2 pg/ml, P < 0.05). Baseline serum CoQ levels (0.21 +/- 0.11 vs. 0.19 +/- 0.10 microg/ml) were low; however, after 12 weeks, serum CoQ showed a significant increase in the carni Q-gel group as compared to the control group (2.7 +/- 1.2 and 0.76 +/- 0.14 microg/ml, respectively). After 12 weeks of treatment, the quality of life visual analogous scale revealed that dyspnoea, palpitation and fatigue, (NYHA class II-III-IV), which were present at rest in all patients at baseline, showed beneficial effects in the intervention group compared to the placebo group. The six-minute walk test showed that there was a significant greater benefit in walking, from the baseline distance in the intervention group (208 +/- 15.8 vs. 281 +/- 20.6 metres, P < 0.02) compared to the placebo group (218.4 +/- 17.6 vs. 260.7 +/- 19.3 metres, P < 0.05). The symptom scale indicated that the majority of patients showed improvement in the intervention group compared to the control group (28 vs. 16 patients, respectively, P < 0.05).Three patients in the intervention group had nausea and vomiting, which were controlled with symptomatic treatment. CONCLUSIONS: These findings indicate that treatment with ubiquinol + L-carnitine can cause a significant reduction in the pro-inflammatory cytokines that are neurohumoural precursors related to sympathetic and parasympathetic activity, which is impaired in patients with heart failure. There was no adverse effect on IL-10. There was a significant improvement in quality of life as well as decrease in NYHA-defined heart failure.     

Hyperimmunoglobulinemia in HIV-1 infected individuals does not clearly correlate with plasma levels of IL-6.

In this study we evaluated interleukin-6 (IL-6) plasma levels in 80 human immunodeficiency virus type 1 (HIV-1) seropositive (+) individuals and 51 HIV-1 seronegative (-) blood donors. Plasma IL-6, detectable only in a subset of HIV-1(+) individuals (45 of 80) and normal blood donors (28 of 51), was significantly (p less than 0.01) increased in HIV-1(+) subjects 187 +/- 20.5 vs. 86.3 +/- 14 pg/ml). Among HIV-1-infected individuals, ARC/AIDS patients showed the highest IL-6 values (243.3 +/- 43.3 pg/ml). HIV-1(+) subjects showed, at all the different stages of the disease, a significant increase in total gammaglobulins, particularly IgG (2071 +/- 101 vs 1265 +/- 34 of HIV-1 seronegative controls). Although among HIV-1-infected individuals, the group with detectable plasma levels of IL-6 shows the highest levels of IgG (2243 +/- 146 vs. 1790 +/- 105, p less than 0.05), no positive correlations were observed between plasma levels of IL-6 and total gamma globulins (r = 0.2) or IgG (0.17). IL-6 production was also examined in the endotoxin-free supernatants of peripheral blood cultured monocytes and CD4+ T lymphocytes, in the presence or absence of specific stimuli. The amount of IL-6 released in monocyte and CD4+ T-lymphocyte culture supernatants was similar in 40 HIV-1(+) individuals and 35 HIV-1(-) controls. Our data show that plasma levels of IL-6 are significantly increased in HIV-1-infected individuals, in particular in ARC/AIDS patients. However, such an increase does not strictly correlate with the degree of hypergammaglobulinemia in the same HIV-1-infected individuals.     

Comparison of serum levels of inflammatory markers and allelic variant of interleukin-6 in patients with acute coronary syndrome and stable angina pectoris

OBJECTIVES: Although the relationship between atherosclerosis and inflammatory cells has been recognized in recent years, the effect of interleukin-6 (IL-6) genetic variants associated with atherosclerosis is still controversial. Therefore, we investigated the association between IL-6 polymorphism and levels of IL-6 in patients with coronary artery disease (CAD). METHODS: We conducted a case-control study on 294 unrelated participants who were referred to the cardiology department of the university hospital for coronary angiography because of suspected ischemic heart disease. Group I comprised patients with clinically acute coronary syndrome, and group II comprised patients (individuals matched for age and sex) with clinically stable angina pectoris; both groups were categorized, based on their angiographic findings, as either having angiographically documented less extensive CAD (1 vessel narrowed) or extensive CAD (> or =2 vessels narrowed). They were studied to examine effect of the IL-6 gene variants in CAD. Genotyping was determined by polymerase chain reaction. RESULTS: The IL-6 G/C-174 polymorphism was found in 19 of 106 (18%) in group I and in four of 188 (2%) in group II (P<0.001). Median IL-6 levels were significantly higher in group I (6.7+/-13.6 pg/ml) than in group II (4.1+/-3.8 pg/ml) (P<0.05). In addition, high sensitivity C-reactive protein levels were significantly higher in group I (8.2+/-6.2 mg/dl) than in group II (4.6+/-3.4 mg/dl) (P<0.001). CONCLUSION: These results demonstrated that the presence of the IL-6 G/C-174 polymorphism and increased IL-6 and high sensitivity C-reactive protein levels are strongly associated with the inflammatory system and the course of clinical and hemodynamically significant CAD.     

Endotoxin, TNF-alpha, interleukin-6 and parameters of the cellular immune system in patients with intraabdominal sepsis.

The correlation of endotoxin (ET), tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and cellular immune parameters with multiple organ failure and lethal outcome in intraabdominal infections was studied in a group of 18 patients with peritonitis, abscess or pancreatitis. Of these patients, 7 developed respiratory failure and 5 died due to multiple septic organ failure. The peak levels of ET (2.7 +/- 1.3 ng/ml) in the course of the disease were followed by moderate increases of TNF-alpha (mean 147 +/- 41 pg/ml) and IL-6 (170 +/- 61 pg/ml) within 2 days. Analysis of the parameters for the last 12 days prior to death or discharge showed, that the patient group with lethal outcome was characterized by significant lower mean plasma levels of TNF-alpha (less than 75 pg/ml versus greater than 160 pg/ml) and IL-6 (less than 130 pg/ml versus greater than 270 pg/ml), as well as high rates of unstimulated thymidine uptake into peripheral mononuclear blood cells (greater than 44000 cpm/8 x 10(6) PMBC/18 h versus less than 24000 cmp), T-lymphocyte depression (CD3; approximately greater than 40% reduction) with lower T-helper/inducer subset cell numbers (mean CD:CD8 ratio 1.0 +/- 0.55 versus 1.8 +/- 0.2) and lower lectin (PHA) stimulation values (1.9 +/- 1.4 versus 4.1 +/- 1.0). These data demonstrate an anergic immune status with low mediator levels and depressed T-lymphocyte function in patients with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

霉菌性阴道炎患者体内真菌分布、T淋巴细胞及相关细胞因子水平变化特点及意义

目的探讨霉菌性阴道炎患者体内真菌分布、T淋巴细胞及炎性细胞因子水平变化特点及意义。方法选取2017年1月—12月在我院治疗的霉菌性阴道炎患者182例作为观察组,同时选取女性健康志愿者110例作为对照组,检测2组受试者阴道分泌物中T淋巴细胞及细胞因子水平,同时对观察组阴道分泌物进行真菌培养。结果 182例患者中,病原菌以白色念珠菌为主,占43.41%;观察组阴道分泌物CD3~+、CD4~+和CD8~+T淋巴细胞水平分别为(52.12±10.45)%、(33.30±8.23)%和(25.10±9.22)%,明显低于对照组(P均0.05);观察组阴道分泌物IL-2、TNF-α和IFN-γ分别为(7.21±1.42)pg/ml、(17.90±4.55)pg/ml和(19.81±4.50)pg/ml,明显低于对照组(P均0.05),而IL-4和IL-10分别为(40.32±8.33)pg/ml和(25.66±4.33)pg/ml,明显高于对照组(P均0.05);复杂性霉菌性阴道炎患者阴道分泌物CD3~+、CD4~+、CD8~+T淋巴细胞以及IL-2、TNF-α和INF-γ水平明显低于普通霉菌性阴道炎患者(P均0.05),而IL-4和IL-10明显高于普通霉菌性阴道炎患者(P均0.05)。结论霉菌性阴道炎病原体以白色念珠菌为主,Th1/Th2细胞介导的细胞免疫参与了疾病过程。     

急性冠状动脉综合征患者血管因子与冠状动脉斑块特征的相关性研究

目的探讨急性冠状动脉综合征（ACS）患者血管因子与冠状动脉斑块特征的相关性。方法选择56例ACS患者,年龄（60±11）岁,男37例,女19例,发病时取血,应用液相蛋白芯片结合流式细胞分析方法测定7种血管因子：可溶的P选择素（sPE）、组织血纤维蛋白溶酶原激活物（tPA）、单核细胞趋化蛋白1（MCP-1）、白细胞介素（IL）-8、IL-6、可溶的血管细胞间黏附分子1（sVCAM-1）和可溶的黏附分子40配体（sCD40L）,以及相应的炎症因子;常规冠状动脉造影,并用血管内超声（IVUS）检测56个靶病变处动脉粥样斑块形态学及性质特征。分析急性心肌梗死（AMI）与不稳定性心绞痛（UA）患者、易损斑块与非易损斑块组发生斑块破裂时的血管因子改变以及斑块形态学指标与血管因子的相关性。结果存在密切相关的血管因子有sVCAM-1和sPE、sVCAM-1和sCIMOL、sCD40L和sPE、IL-6和IL-8、IL-8和MCP1、以及MCP1和sVCAM-1;易损斑块组的高敏C反应蛋白（hs-CRP）为（18．9±4．9）mg／L,IL-6为[19.5ng／L（9．2—44．6ng／L）],明显高于非易损斑块组[hs-CRP：（5.8±3．6）mg／L,IL-6：5.3ng／L（2．3—13．4ng／L）,均P〈0．05];与非斑块破裂组比较,斑块破裂组的sCD40L[（474±126）ng／L比（238±35）ng／L],sPE[（107．2±39．9）ng／L比（49．1±5．6）μg／L]和MCP-1[（132±18）ng／L比（127±13）ng／L]明显升高（均P〈0．05）;tPA与斑块形态之间存在一定的相关性（均P〈0．05）。sCIMOL、MCP—1,sPE和TC水平升高是发生斑块破裂的独立危险因素（均P〈0．05）。结论炎症反应作为中间过程,IL-6和CRP标志易损斑块的生物特点,对AMI可能有一定的诊断意义,而sCIMOL、MCP-1和sPE可能是另一个潜在的反映ACS严重发作的标志。     

冠心病患者分泌型磷脂酶A2的变化及其与白细胞介素8、溶血磷脂酸的关系

目的了解冠心病患者分泌型磷脂酶 A2(sPLA2)的变化,并通过测定 IL-8、LPA 等相关细胞因子,对 sPLA2的作用机制进行初步探讨。方法冠状动脉造影确诊的262例患者,其中急性冠脉综合征(ACS)110例,稳定性冠心病(SCHD)63例,正常患者89例,分别测定 sPLA2、白细胞介素8(IL-8)、高敏 C 反应蛋白(hs-CRP)和溶血磷脂酸(LPA)水平,并进行对比分析。结果冠心病患者sPLA2[(68±17)U/ml]、IL-8[(182±80)pg/ml]以及 LPA[(2.85±0.36)μmol/L]均明显高于对照组[sPLA2:(55±12)U/ml,IL-8:(119±33)pg/ml,LPA:(2.34±0.36)μmol/L,均 P<0.01],其中ACS 组的 sPLA2[(71±18)U/ml]、IL-8[(195±78)pg/ml]也明显高于 SCHD 组[sPLA2:(63±12)U/ml],IL-8:[(159±79)pg/ml,均 P<0.01;sPLA2与 IL-8(r=0.203,P=0.007)、LPA(r=0.658,P<0.01)、hs-CRP(r=0.231,P=0.005)均呈正相关;sPLA2≥63.75 U/ml 时,患冠心病的相对危险度为6.248(P<0.01)。结论冠心病患者 sPLA2明显升高,它可能与 IL-8共同参与冠心病的炎症发展过程,并与下游相关产物 LPA 进一步加速其进展。提示 sPLA2升高是冠心病的独立危险因素之一。     

持续吸入变应原引起支气管哮喘小鼠免疫耐受

目的探讨吸入变应原引起支气管哮喘(简称哮喘)过敏性气道炎症免疫耐受形成的机制。方法BALB/c小鼠60只,按随机数字表法分为实验组(50只)和空白对照组(10只),实验组小鼠先给予腹腔注射卵清白蛋白(OVA)1mg,每周1次,共3周。雾化吸入OVA每天1h(含OVA80μg),连续10d。依据吸入OVA时间分为A、B、C、D、E5组,每组10只。A组雾化吸入10d后处死。B、D组继续每天1次,每次1h,每周5次,分别吸入OVA4周及8周,然后每天1h,连续10d吸入OVA后处死。C组停止吸入OVA4周后再次吸入OVA,每天1h,连续10d后处死。E组每天1次,每次1h,每周5次,吸入OVA4周,停止雾化吸入OVA4周,然后每天1h,连续10d吸入OVA后处死。测定各组小鼠支气管肺泡灌洗液(BALF)中细胞总数,嗜酸粒细胞、淋巴细胞、CD4+、CD8+、CD4+IL-10+分类及BALF中白细胞介素4(IL-4)、γ干扰素(IFN-γ)、IL-10的含量。测定血清中IL-4、IFN-γ、IL-10、OVA、IgE、IgG1、IgG2a水平,并对各组小鼠肺组织病理学进行分析。结果空白对照组BALF中嗜酸粒细胞、B淋巴细胞、CD4+IL-10+细胞分别为0.010±0.000、2.1±1.9、4.9±1.5,A组分别为0.480±0.110、5.1±2.6、5.1±2.3,B组分别为0.120±0.020、8.9±3.6、10.4±3.6,C组分别为0.560±0.050、4.7±1.7、6.3±3.1,D组分别为0.070±0.030、10.1±2.9、12.7±4.5,E组分别为0.680±0.030、5.6±3.2、6.1±3.4,各组间比较差异有统计学意义(F值分别为36.46、31.89、167.89,P均<0.01)。B、D组BALF中CD4+IL-10+细胞数与A组比较差异有统计学意义(q=5.8、6.4,P均<0.05);空白对照组BALF中IL-4、IL-10水平分别为(21±3)pg/ml、(44±12)pg/ml,A组分别为(128±23)pg/ml、(68±18)pg/ml,B组分别为(54±12)pg/ml、(127±27)pg/ml,C组分别为(133±21)pg/ml、(78±17)pg/ml,D组分别为(8±18)pg/ml、(135±34)pg/ml,E组分别为(143±26)pg/ml、(76±15)pg/ml,组间比较差异有统计学意义(F分别为37.20、143.78,P均<0.01)。B、D两组BALF中IL-10水平与A组比较差异有统计学意义(q分别为7.8、9.6,P均<0.05)。结论持续吸入变应原可使小鼠气道炎症减轻,产生免疫耐受,调节T淋巴细胞产生的IL-10参与了耐受形成。     

Entecavir up-regulates dendritic cell function in patients with chronic hepatitis B

AIM： To investigate the in vitro effect of entecavir （ETV on the function of dendritic cells （DCs） derived from chronic hepatitis B （CHB） patients. METHODS： Mononuclear cells were isolated from peripheral blood of patients with CHB. DCs wer incubated with RPMI-1640 medium supplemented wit fetal bovine serum, IL-4, granulocyte-macrophag colony-stimulating factor （GM-CSF）. DCs were treate with or without ETV on the fourth day. Cell surfac molecules, including CD1a, CD80, CD83 and HLA-DR were assessed by flow cytometry. Concentrations of IL- and IL-12 in the supernatant were assayed by enzyme linked immunosorbent assay （ELISA）. The ability of th generated DCs to stimulate lymphocyte proliferation wa observed. RESULTS： Compared with CHB control group, th expression levels of CD1a （29.07 ± 3.20 vs 26.85 ± 2.80 CD83 （25.66 ± 3.19 vs 23.21 ± 3.10）, CD80 （28.00 ± 2.7 vs 25.75 ± 2.51） and HLA-DR （41.96 ± 3.81 vs 32.20 ± 3.04） in ETV-treated group were higher （P 〈 0.05）. ETV treated group secreted significantly more IL-12 （157.6 ± 26.85 pg/mL vs 132.60 ± 22.00 pg/mL （P 〈 0.05） an had a lower level of IL-6 in the culture supernatant （83.0 ± 13.88 pg/mL vs 93.60 ± 13.61 pg/mL, P 〈 0.05） tha CHB control group. The ability of DCs to stimulate th proliferation of allogeneic lymphocytes was increase in ETV-treated group compared with CHB control grou （1.53 ± 0.09 vs 1.42 ± 0.08, P 〈 0.05）.CONCLUSION： Entecavir can enhance the biological activity of DCs derived from CHB patients.     

Relation between CD4+ T-cell activation and severity of chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

The percentage of CD4(+) T cells in blood is correlated with left ventricular dysfunction and decreased ejection fraction in heart disease. The aim of this study was to determine the relation between activation of CD4(+) T cells and New York Heart Association functional classes in chronic heart failure (HF) and differences in inflammatory activation between ischemic cardiomyopathy (IC) and idiopathic dilated cardiomyopathy (IDC). Blood samples were obtained from 47 patients with HF and 20 controls. Percentages of interferon-gamma-positive CD4(+) T cells (representative type 1 T-helper cells) and interleukin-4-positive CD4(+) T cells (representative type 2 T-helper cells) were analyzed using 3-color flow cytometry. The proportion of interferon-gamma-positive CD4(+) T cells was higher in patients with HF (28.96 +/- 12.90%) than in controls (18.12 +/- 5.28, p = 0.0006), but there was no difference in percentage of interleukin-4-positive CD4(+) T cells between the 2 groups. The proportion of interferon-gamma-positive CD4(+) T cells and plasma B-type natriuretic peptide levels increased with worsening of New York Heart Association functional class in the IC and IDC groups. The proportion of interferon-gamma-positive CD4(+) T cells in the IC group (33.88 +/- 13.33%) was higher than in the IDC group (22.33 +/- 8.88%, p = 0.002); however, plasma B-type natriuretic peptide levels were higher in the IDC group (358.0 pg/ml, 327.5 to 1,325.7) than in the IC group (82.7 pg/ml, 34.7 to 252.9, p = 0.019). In conclusion, we demonstrated pronounced type 1 T-helper cell activation in patients with HF in proportion to severity of HF and that the specificity of T-cell activation differs between patients with IC and those with IDC.     

Elevated interleukin-1beta in pericardial fluid of patients with ischemic heart disease.

BACKGROUND: Inflammatory cytokines may play an important role in the pathogenesis of atherosclerosis and heart failure. We have previously demonstrated that long-term treatment with interleukin (IL)-1beta in the coronary artery and myocardium promotes coronary arteriosclerosis and impairs cardiac function, respectively. The cytokines in pericardial fluid may reflect the extent of coronary atherosclerosis and may also directly promote the atherosclerotic process. This study was designed to examine the significance of cytokine concentrations in pericardial fluid of patients with cardiovascular disease. METHODS: We measured concentrations of 10 major cytokines in the pericardial fluid of 56 consecutive patients obtained during open heart surgery, 27 with ischemic heart disease (IHD group), 21 with valvular heart disease (VHD group) and eight with congenital heart disease (CHD group). RESULTS: The pericardial concentrations of IL-1beta (pg/ml) were significantly higher in the IHD group (60 +/- 15) than in the VHD (29 +/- 5) or the CHD group (26 +/- 4) (P < 0.05 both). There was no significant difference in pericardial concentrations of other cytokines among the three groups. In the IHD group, the IL-1beta concentrations were significantly elevated in patients who had undergone emergency operations or in those with unstable angina. CONCLUSIONS: These results suggest that pericardial concentrations of IL-1beta may reflect the extent of ischemic heart disease and that elevated IL-1beta concentrations in pericardial fluid may also directly promote the process of coronary atherosclerosis.     

Increased serum concentrations of interleukin-1 beta in patients with coronary artery disease.

OBJECTIVE: To assess serum interleukin-1 beta (IL-1 beta) concentrations in patients with ischaemic heart disease, to characterise subgroups of patients with raised IL-1 beta concentrations, and to examine whether serum IL-1 beta concentrations correlate with non-specific indices of inflammation. DESIGN: Survey study of patients with ischaemic heart disease. SETTING: Cardiac catheterisation laboratory of a tertiary medical centre. PATIENTS: Consecutive patients with angina pectoris and patients recovering from uncomplicated acute myocardial infarction and undergoing elective coronary angiography. RESULTS: Mean(SD) serum IL-1 beta concentrations were higher (P < 0.001) in patients with angina and < 50% coronary artery stenosis (n = 11; 18.8(19.9) pg/ml), patients with angina > or = 50% stenosis (n = 23; 10.2(11.4) pg/ml), and patients 8(0.8) days post-infarction (n = 13; 4.4(5.8) pg/ml) than in 15 healthy, age-matched controls (0.3(0.5) pg/ml). Serum IL-1 beta concentrations did not correlate with total blood leucocyte counts (r = -0.07, P = NS), blood lymphocyte counts (r = -0.24, P = NS), and blood monocyte counts (r = -0.29, P = NS), or with fibrinogen (r = -0.16, P = NS) and C-reactive protein concentrations (9(10.5) mg/dl v 14.1(19) mg/dl for patients with undetectable and detectable concentrations, respectively, P = NS). CONCLUSION: Serum IL-1 beta concentrations are raised in patients with ischaemic heart disease, in particular in those with minimal coronary artery disease and angina. The precise role of IL-1 beta in coronary artery disease remains to be determined.