Diagnostic value of interleukin-1alpha, interleukin-6, and tumor necrosis factor in pleural effusions

STUDY OBJECTIVES: Interleukin (IL)-1alpha, IL-6, and tumor necrosis factor (TNF)-alpha were measured in pleural fluid from 57 patients with pleural effusion in order to evaluate the diagnostic utility of these cytokines. We studied 20 patients with malignant pleural effusion, 11 patients with parapneumonic pleural effusion, 9 patients with tuberculous pleural effusion, and 17 patients with transudative pleural effusion. Cytokines were measured by radioimmunoassay. SETTING: University tertiary hospital. RESULTS: The mean values of the three cytokines measured in pleural fluid or in serum were significantly higher in patients with exudates than with transudates (p < 0.05). The ratio of IL-6 in pleural fluid to serum was significantly higher in exudates than in transudates (p < 0.05). The level of IL-6 in pleural fluid was significantly higher in tuberculous than malignant (p < 0.007) or parapneumonic pleural effusions (p < 0.04). No significant difference between the three types of exudates was found in pleural fluid levels of IL-1alpha or TNF-alpha. CONCLUSIONS: Serum levels of IL-1alpha, TNF-alpha, and in particular IL-6 can distinguish exudates from transudates, while pleural fluid IL-6 levels could be useful as an additional marker in the differential diagnosis of tuberculous, malignant, and parapneumonic exudates. Finally, our results suggest that there is local cytokine production in exudative pleural effusions.     

Role of pleural viscosity in the differential diagnosis of exudative pleural effusion

OBJECTIVE AND BACKGROUND: Determining the aetiology of an effusion involves assessing if it is an exudate or a transudate. However, a reliable test for determining the aetiology of a pleural effusion is lacking. Pleural viscosity has a high sensitivity and specificity and a high positive and negative predictive value for discriminating exudative and transudative pleural effusions. The aim of this study was to use pleural fluid viscosity to discriminate between various aetiologies of exudative effusions, namely malignant, parapneumonic and tuberculous. METHODS: Seventy consecutive patients (24 women, 46 men, mean age = 67 years) with exudative pleural effusion due to pneumoniae in 24 patients, tuberculous pleurisy in 21 and lung cancer in 25 were studied prospectively. Measurements of pleural fluid and plasma viscosity were performed using Brookfield DV-II viscometer. RESULTS: Pleural viscosity and pleural LDH were highest in the tuberculous pleurisy patients and lowest in the lung cancer patients. Pleural viscosity > or = 1.57 was found to be indicative of tuberculous pleurisy with a sensitivity of 100% and specificity of 95%. Pleural viscosity < 1.39 was found to be indicative of lung cancer with a sensitivity of 100% and specificity of 94%. Pleural viscosity was significantly correlated with pleural albumin (r = 0.34, P = 0.004), protein (r = 0.40, P = 0.001), LDH (r = 0.70, P < 0.001) and plasma viscosity (r = 0.44, P < 0.001), having the most significant value with pleural LDH. CONCLUSION: The pleural fluid viscosity of patients with parapneumonic, tuberculous and malignant effusions are significantly different from each other. Among these groups, tuberculous effusions had the highest viscosity, and malignant effusions from lung cancer the lowest.     

Use of pleural fluid C-reactive protein in diagnosis of pleural effusions

The aims of the study were to assess whether C-reactive protein (CRP) is a sensitive marker for discriminating between transudative and exudative and pleural effusions to evaluate whether it can be used to distinguish inflammatory pleural effusions from other types of effusion. Pleural fluid and serum CRP levels were obtained in 97 patients with pleural effusion, using an immunoturbidimetric method (Olympus AU-600 autoanalyser). We compared CRP levels between transudates and exudates, inflammatory effusions and other types of effusion. According to the criteria used, 16 patients were included in the transudate group and 81 patients in the exudate group. Pleural fluid CRP levels were significantly lower in the transudate group (P<0.04; 14.9 +/- 4.9 mg l(-1) and 35.5 +/- 4.9 mg l(-1) respectively). Also, the ratio of pleural fluid to serum was significantly lower in the transudate group (P<0.009; 0.8 +/- 0.5 mg l(-1) and 2.8 +/- 0.7 mg l(-1), respectively). In the exudate group, 35 patients had neoplastic effusions, 10 chronic non-specific pleurisy, 19 tuberculous pleurisy, 16 parapneumonic effusion and one Dressler Syndrome. When these sub-groups were compared, the parapneumonic effusion subgroup CRP levels (mean 89 +/- 16.3 mg l(-1)) were significantly higher than those in the other subgroups, other exudate of neoplastic effusion, tuberculous pleurisy and chronic non-specific effusion and the transudate group (P<0.0001; P<0.0001; P<0.0004 and P<0.0001, respectively). The ratio between pleural fluid and serum CRP was significantly higher in the parapneumonic effusion subgroup than in the neoplastic subgroup (P<0.0002; 6.6 +/- 2.7 mg l(-1) and 1 +/- 0.2 mg l(-1), respectively). Pleural fluid CRP levels > 30 mg l(-1) had a high sensitivity (93.7%) and specificity (76.5%) and a positive predictive value of 98.4%. In the differential diagnosis of pleural effusions, higher CRP levels may prove to be a rapid, practical and accurate method of differentiating parapneumonic effusions from other exudate types. Although the high level of CRP obtained in the exudate group may be due to the number of patients with parapneumonic effusion who were included, the pleural CRP level may also be helpful in discriminating between exudative and transudative pleural effusions.     

Proinflammatory cytokines and fibrinolytic enzymes in tuberculous and malignant pleural effusions

OBJECTIVES: To measure tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in pleural effusions caused by tuberculosis (TB) and malignancy and their relationship with plasminogen activator inhibitor type I (PAI-1) and tissue type plasminogen activator (tPA), and to compare the differences between tuberculous and malignant pleural effusions. In addition, the relationship between the effusion levels of these parameters and the development of residual pleural thickening was evaluated in the patients with tuberculous pleurisy. DESIGN: Prospective study. MATERIALS AND METHODS: TNF-alpha, IL-1beta, PAI-1, and tPA were measured simultaneously in blood and pleural fluid using an enzyme-linked immunosorbent assay in 33 patients with tuberculous and in 30 patients with malignant pleural effusions. Residual pleural thickening was measured and defined as a pleural thickness of >/= 10 mm found on chest radiographs at the completion of anti-TB chemotherapy in tuberculous pleurisy patients. RESULTS: In both groups, the levels of proinflammatory cytokines and fibrinolytic enzymes were significantly higher in pleural fluid than in blood. The levels of TNF-alpha and PAI-1 were significantly higher in tuberculous than in malignant effusions. In contrast, malignant pleural fluid had significantly higher values of tPA than did tuberculous pleural fluid. In tuberculous effusions, the values of PAI-1 and the PAI-1/tPA ratio correlated positively and the levels of tPA correlated negatively with those of TNF-alpha and IL-1beta. In malignant pleural fluid, positive correlations were found between the values of proinflammatory cytokines (TNF-alpha and IL-1beta) and PAI-1. Residual pleural thickening was found in 9 of 33 patients (27. 3%) with tuberculous pleurisy. The pleural fluid values of TNF-alpha, IL-1beta, and PAI-1 were significantly higher and the concentrations of tPA were significantly lower in tuberculous pleurisy patients with residual pleural thickening. CONCLUSIONS: Compared to malignant pleural effusion, fibrinolytic activity in pleural fluid was reduced in tuberculous effusion. Pleural inflammation caused by TB may enhance the release of proinflammatory cytokines, particularly TNF-alpha, which subsequently may increase PAI-1 and decrease tPA in pleural fluid. The imbalance of PAI-1 and tPA in pleural space may lead to fibrin deposition and pleural thickening.     

Discrimination of exudative pleural effusions based on multiple biological parameters.

Pleural effusion is a common complication of various diseases. Conventional methods are not always capable of establishing the cause of pleural effusion, so alternative tests are needed. The aim of this study was to explore means of discriminating between different pleural effusion groups, malignant, parapneumonic and tuberculous, based on the combined function of seven biological markers. Adenosine deaminase (ADA), interferon-gamma, C-reactive protein (CRP), carcinoembryonic antigen, interleukin-6, tumour necrosis factor-alpha and vascular endothelial growth factor concentration levels were measured in pleural fluid from 45 patients with malignant, 15 with parapneumonic and 12 with tuberculous pleural effusion. Receiver operating characteristic curve analysis, multinomial logit modelling and canonical variate analysis were applied to discriminate the pleural effusion groups. The three groups could be discriminated successfully using the measured markers. The most important parameters for discrimination were ADA and CRP concentration levels. An individual with an ADA concentration level of >45 U.L(-1) and a CRP concentration of <4 mg.dL(-1) was more likely to belong to the tuberculous pleural effusion group, whereas one with an ADA concentration level of <40 U.L(-1) and a CRP concentration of >6 mg.dL(-1) was more likely to belong to the parapneumonic pleural effusion group, and one with a CRP concentration of <4 mg.dL(-1) to the malignant pleural effusion group. The combination of adenosine deaminase and C-reactive protein levels might be sufficient for discriminating between the three different groups of exudative pleural effusion: malignant, tuberculous and parapneumonic.     

Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions.

Adenosine deaminase (ADA) can aid in the diagnosis of tuberculous pleural effusions, but false-positive findings from lymphocytic effusions have been reported. The purpose of this study is to assess the ADA levels in nontuberculous lymphocytic pleural effusions (lymphocyte count > 50%) of different aetiologies. Altogether, 410 nontuberculous lymphocytic pleural fluid samples were consecutively selected. These included malignant effusions (n = 221), idiopathic effusions (n = 76), parapneumonic effusions (n = 35), postcoronary artery bypass graft surgery effusions (n = 6), miscellaneous exudative effusions (n = 21) and transudative effusions (n = 51). The ADA level reached the diagnostic cut-off for tuberculosis (40 U x L(-1)) in seven of the 410 cases (1.71%). The negative predictive value of ADA for the diagnosis of pleural tuberculosis was 99% (403 of 407 cases) in the group of lymphocytic pleural effusions. In five of these seven patients ADA1 and ADA2 were measured, and in all these cases (100%) ADA1/ADA(p) correctly classified these lymphocytic effusions as nontuberculous (ratio < 0.42). This prospective study provides additional evidence that adenosine deaminase levels in nontuberculous lymphocytic pleural effusions seldom exceed the cut-off set for tuberculous effusions. The pleural fluid adenosine deaminase levels were significantly higher in different types of exudative effusions than in transudates. An adenosine deaminase level < 40 IU x L(-1) virtually excluded a diagnosis of tuberculosis in lymphocytic pleural effusions. Adenosine deaminase1/adenosine deaminase(p) correctly classified all nontuberculous lymphocytic pleural effusions with high adenosine deaminase levels.     

Accuracy of chest sonography and polymorphonuclear elastase in the assessment of bacterial pleural effusion

Background: The relationship between chest sonography findings and inflammatory markers for assessing bacterial pleural effusion is not well established. We decided to study the accuracy of chest sonography in determining the nature of bacterial pleural effusion and its relationship with polymorphonuclear elastase (PMN-E) results. Methods: Pleural sonography and PMN-E were evaluated in a prospective study of 144 consecutive patients with pleural effusion of various etiologies: 25 complicated parapneumonic, 18 uncomplicated parapneumonic, 33 tuberculous, 17 malignant, 12 transudates, and 39 of unknown etiology. The sonographer distinguished between anechoic and septated pattern. The relationship between sonographic appearance and inflammatory markers was evaluated. Results: All of the complicated parapneumonic, 11 uncomplicated parapneumonic, and 28 tuberculous effusions were septated. Septated pattern and PMN-E value were independent predictors of infectious pleural disease (p <0.05). The simultaneous presence of a septated pattern and a PMN-E higher than 100 microg/l had a sensitivity of 79.1% and a specificity of 91.1% for the diagnosis of bacterial effusions. Conclusions: PMN-E level and the sonographic pattern of pleural fluid may be useful in the diagnosis of bacterial pleural effusions.     

Childhood parapneumonic effusions: biochemical and inflammatory markers

STUDY OBJECTIVES: Biochemical and inflammatory markers in pleural inflammation were evaluated in pediatric cases of parapneumonic effusions, and interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha concentrations were tested for possible differentiation of the complicated nature of effusions. PATIENTS: Twenty-eight patients (12 female) who were admitted to Hacettepe University Childrens' Hospital over a 2-year period were included in the study. MEASUREMENTS: Patients were grouped according to the stage of effusion. Pleural fluid leukocyte count, neutrophil ratio, pH, protein, glucose levels, lactate dehydrogenase (LDH) levels, TNF-alpha levels, IL-8 levels, and nitrite levels were obtained. RESULTS: Of these patients, 13 had empyema, 10 had complicated parapneumonic effusions (CPEs), and 5 had uncomplicated parapneumonic effusions (UPEs). Protein and glucose levels decreased, leukocyte count, neutrophil ratio, TNF-alpha levels, nitrite levels, and IL-8 levels increased progressively as the stage of the disease progressed. IL-8 levels, but not TNF-alpha and nitrite levels, were statistically different among the groups. IL-8, TNF-alpha, and nitrite levels all correlated positively with each other (all p < or = 0.001), and pH correlated negatively with these markers (all p < or = 0.001). At a cutoff value of 76.6 pg/mL, TNF-alpha discriminated between CPEs and UPEs with a sensitivity of 50%, a specificity of 100%, and an accuracy of 78%. At a cutoff value of 701.6 pg/mL, IL-8 differentiated CPE and UPE with a sensitivity of 80%, a specificity of 80%, and an accuracy of 86%. CONCLUSIONS: Progressive changes in common biochemical markers (ie, pH, and protein, glucose, and LDH levels) are interrelated during stages of pleural inflammation. IL-8 may be used as an alternative marker for discriminating between CPEs and UPEs in pediatric parapneumonic effusions.     

Pleural fluid interleukin-8 and C-reactive protein for discriminating complicated non-purulent from uncomplicated parapneumonic effusions

Background and objective:   This study was designed to test the hypothesis that measurement of IL-8 and CRP in pleural fluid could improve the identification of patients with non-purulent parapneumonic effusions that ultimately require chest tube drainage.
Methods:   We assessed IL-8, CRP and three classical parameters (pH, glucose and LDH) in the pleural fluid of 100 patients with parapneumonic effusions. Forty-nine of these patients had non-purulent complicated effusions (complicated parapneumonic pleural effusion, CPPE), and 51 had uncomplicated parapneumonic pleural effusions (UPPE). Receiver-operating characteristic curves were used to assess the sensitivity and specificity of pleural fluid biochemical parameters for differentiating among the two patient groups. IL-8 production was determined using a commercially available ELISA kit, and CRP was measured by immunoassay.
Results:   At a cutoff value of 1000 pg/mL, IL-8 differentiated CPPE from UPPE with a sensitivity of 84% and a specificity of 82%. Likewise, CRP levels were higher in CPPE than in UPPE, and showed 72% sensitivity and 71% specificity at a cutoff value of 80 mg/L. We found that all five pleural fluid tests showed similar diagnostic accuracies when evaluated by receiver-operating characteristic analysis. However, multivariate analysis indicated that the size of the effusion, as well as pleural fluid pH and IL-8 concentration, were the best discriminatory parameters, with likelihood ratios of 6.4, 4.4 and 3.9, respectively.
Conclusions:   Pleural fluid IL-8 is an accurate marker for the identification of non-purulent CPPE.     

Interleukin-8 is a major neutrophil chemotactic factor in pleural liquid of patients with empyema.

Interleukin-8 (IL-8), a potent neutrophil chemotactic peptide, has been found in association with human disease, but its contribution to chemotactic activity in humans is not yet known. We asked whether IL-8 is present in inflammatory human pleural effusions, and to what extent it contributes to pleural liquid neutrophil chemotactic activity. Because tumor necrosis factor alpha (TNF-alpha) is a strong inducer of IL-8, we also asked whether TNF-alpha was present. For this prospective study, we collected pleural liquid from 51 patients (empyema, 14; parapneumonic, four; tuberculous, eight; malignant, nine; miscellaneous exudative, seven; and transudative, nine), counted pleural neutrophils, and measured IL-8 and TNF-alpha concentrations in the supernatant. To determine the contribution of IL-8 to chemotactic activity in empyema, we measured the neutrophil migration induced by empyemic liquids before and after addition of anti-IL-8 F(ab')2 antibody fragments or control anti-IL-6 F(ab')2. We found that IL-8 concentrations were higher in empyema (61.3 +/- 21.0 ng/ml [SEM]) than in all other effusions (1.1 +/- 0.5 ng/ml) (p = 0.0001). All empyema liquids had IL-8 concentrations above 2.5 ng/ml, which was true for only three of the other 37 effusions (two parapneumonic, one tuberculous). IL-8 levels correlated with the pleural neutrophil count (r = 0.46; p = 0.007) and the neutrophil chemotactic activity of pleural liquid (r = 0.43; p = 0.008). Anti-IL-8 antibodies decreased chemotactic activity in empyema liquids by 65 +/- 5%, whereas the control antibody had no effect (0 +/- 5% decrease) (p = 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. METHODOLOGY: Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. RESULTS: In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. CONCLUSIONS: In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.     

Vascular endothelial growth factor and proinflammatory cytokines in pleural effusions

To evaluate the predictive value of vascular endothelial growth factor (VEGF) in the differential diagnosis of pleuritis and its association with other proinflammatory cytokines in pleural effusion, we measured VEGF together with interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha) and soluble intercellular adhesion molecule-1 (sICAM-1) in pleural effusions. We investigated 127 patients with pleural effusion (congestive heart failure: 21; parapneumonic: 27; tuberculous: 41; malignant: 38). We examined standard parameters of pleural effusion and measured pleural effusion VEGF, IL-1beta, TNF-alpha and sICAM-1 using enzyme-linked immunosorbent assay. VEGF level was significantly higher in malignant effusion than in other groups. TNF-alpha level was significantly higher in tuberculous pleurisy than in other groups. In tuberculous pleurisy VEGF level showed significant positive correlations with mononuclear cell counts and all investigated cytokines. The sensitivity and specificity of VEGF in the diagnosis of malignancy was 100 and 84%, respectively (cutoff = 2000 pg/ml). The sensitivity and specificity of VEGF and TNF-alpha in the diagnosis of tuberculous pleurisy (VEGF titer <2000 pg/ml and TNF-alpha titer > 55 pg/ml) was 88.9 and 77.1%, respectively. We propose that measurement of VEGF together with TNF-alpha is helpful in differentiating between tuberculous pleurisy and malignant pleural effusion and that VEGF correlates with proinflammatory cytokines especially in tuberculous pleurisy. We also propose that measurement of pleural VEGF is helpful for the diagnosis of malignant pleural effusion.     

腺苷脱氨酶诊断结核性胸膜炎价值的再评价

目的 探讨胸腔积液和血清中腺苷脱氨酶(ADA)对鉴别结核性胸膜炎及恶性胸腔积液的临床价值.方法 回顾性分析91例经内科胸腔镜胸膜活检病理确诊为结核性胸腔积液(结核组49例)和恶性胸腔积液(恶性组42例)患者的胸腔积液及血清中ADA活性,应用受试者工作曲线(ROC曲线)确定结核性胸膜炎患者胸腔积液ADA的最佳临界值.结果 结核组胸腔积液ADA活性和胸腔积液ADA与血清ADA比值分别为(46±26)U/L和4.1±4.0,明显高于恶性组的(16±8)U/L和1.7±1.2,差异均有统计学意义(t值分别为7.383和3.852,均P＜0.01),结核组和恶性组的血清ADA活性分别为(13±5)U/L和(12±6)U/L,差异无统计学意义(t=1.582,P＞0.05).应用ROC曲线确定胸腔积液ADA诊断结核性胸膜炎的最佳临界值为28.7 U/L,灵敏度为75.5%,特异度为95.2%.结论 胸腔积液ADA活性可以作为鉴别结核性和恶性胸腔积液的重要指标,对结核性胸膜炎有较高的临床诊断价值,而血清ADA活性对鉴别两者无临床意义.     

Tumor necrosis factor-alpha in pleural fluid: a marker of complicated parapneumonic effusions

STUDY OBJECTIVES: We sought to determine whether pleural fluid tumor necrosis factor (TNF)-alpha is a more accurate parameter to identify nonpurulent complicated parapneumonic effusion (CPPE) than the classical chemistries, namely pH, glucose, or lactate dehydrogenase (LDH). METHODS: We studied 80 consecutive patients with parapneumonic effusions (35 with uncomplicated parapneumonic effusion [UPPE], 23 with nonpurulent CPPE, and 22 with empyema). Concentrations of standard biochemical parameters together with TNF-alpha were measured in pleural fluid, the latter by using an immunoenzymometric assay. RESULTS: Pleural TNF-alpha was significantly higher in CPPE (133.0 pg/mL) and empyema (142.2 pg/mL) than in UPPE (39.1 pg/mL). A cut-off value of 80 pg/mL for pleural TNF-alpha resulted in a sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of 78%, 89%, and 0.87, respectively, for the diagnosis of nonpurulent CPPE. A multivariate analysis selected both pleural TNF-alpha > or = 80 pg/mL and LDH > or = 1,000 U/L (sensitivity, 74%; AUC = 0.86), but excluded pleural glucose < or = 60 mg/dL (sensitivity, 39%; AUC = 0.82) and pH < or = 7.20 (sensitivity, 41%; AUC = 0.78), for identifying the need for drainage. The combined sensitivity of pleural fluid TNF-alpha and LDH was found to be 91%. CONCLUSIONS: Pleural TNF-alpha may contribute to the identification of patients with nonpurulent CPPE with at least the same diagnostic accuracy, if not better, than the use of pH, glucose, or LDH.     

Assay of pleural fluid interleukin-6, tumour necrosis factor-alpha and interferon-gamma in the diagnosis and outcome correlation of tuberculous effusion

OBJECTIVE: To assess the usefulness of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the diagnosis and prediction of outcome of pleural tuberculosis. PATIENTS AND METHODS: Pleural fluid from 32 TB and 34 non-TB patients was sent for assay of IL-6, TNF-alpha and IFN-gamma. Clinical parameters at presentation and residual pleural scarring at completion of treatment were assessed for pleural TB cases. RESULTS: The pleural fluid Levels of IL-6, TNF-alpha and IFN-gamma in TB patients were significantly higher than those with non-TB effusions (P values of <0.001, 0.018 and <0.001, respectively by independent t-test). Utility of these cytokines for diagnosis of pleural TB was evaluated using receiver operating characteristic (ROC) curve analysis. The cut-off values for IL-6, TNF-alpha and IFN-gamma determined in this analysis were 4000, 4 and 60 pg/ml respectively, and their sensitivity and specificity were 90.6% and 76.5%, 90.6% and 79.4%, 100% and 100%, respectively. The pretreatment pleural fluid IL-6 levels had a positive correlation with the number of febrile days after treatment (Pearson correlation test: r=0.60, P=0.009). A negative correlation was found between the percentage reduction in pleural fluid cytokines after 2 weeks treatment and the extent of residual pleural scarring (IL-6: r=-0.62, P=0.041; TNF-alpha: r=-0.65, P=0.030; IFN-gamma: r=0.83, P=0.002). CONCLUSION: Pleural fluid IL-6, TNF-alpha and IFN-gamma assays are useful in the diagnosis of pleural TB. The initial IL-6 level correlates with the number of febrile days. The percentage change of cytokines after 2 weeks of treatment also helps to predict residual pleural scarring.     

Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions.

The aim of this study was to assess the expression of several metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in exudative pleural effusions, and their relationship with inflammatory and fibrinolytic mediators in parapneumonic effusions. The study included 51 parapneumonic effusions (30 empyema or complicated parapneumonic, 21 noncomplicated parapneumonic), 28 tuberculous, 30 malignant and 30 transudates. Inflammatory markers (tumour necrosis factor-alpha, interleukin-8, polymorphonuclear elastase), fibrinolytic system variables (tissue plasminogen activator (PA), urokinase PA (u-PA), plasminogen activation inhibitor (PAI)-1, PAI-2), and several MMPs (MMP-1, MMP-2, MMP-8, MMP-9) and TIMPs (TIMP-1, TIMP-2) were determined by ELISA in plasma and pleural fluid. Elevated MMP-2 and TIMP-1 concentrations were observed in all the pleural fluid samples studied. The group of empyema or complicated parapneumonic effusions showed higher MMP-1, MMP-8 and MMP-9 concentrations than the remaining exudates. There was no correlation between MMP and TIMP levels in plasma and pleural fluid in this group of effusions. In parapneumonic effusions, MMP-1, MMP-8 and MMP-9 showed a positive correlation with the inflammatory markers and with u-PA and PAI-1. Moreover, there was a relationship between MMP-8 concentration in pleural fluid and pleural thickening at the end of treatment. In conclusion, elevated metalloproteinase-1, -8 and -9 expression was found in parapneumonic pleural effusions. These metalloproteinases could be implicated in the local inflammatory response existing in this group of effusions.     

Cytokine production in patients with tuberculous pericarditis.

SETTING: An academic hospital in the Western Cape, South Africa. OBJECTIVE: To evaluate cytokine production (interferon-gamma [IFN-gamma], interleukin-1 [IL-1], interleukin-2 [IL-2], interleukin-6 [IL-6], interleukin-10 [IL-10], interleukin-4 [IL-4] and tumour necrosis factor-alpha [TNF-alpha]) in patients with tuberculous pericarditis. DESIGN: Subpopulation of a consecutive prospective case series. PATIENTS: Thirty patients presenting with pericardial effusions due to tuberculosis (n = 19), malignancy (n = 6) and non-tuberculous infections (n = 5), and five control subjects who had undergone open heart surgery. RESULTS: The concentration of IFN-gamma was significantly higher in tuberculous pericardial effusions than in the other diagnostic classes (P < 0.0005). The concentration of TNF-alpha was similar in both infective and tuberculous effusions, but was significantly higher than that of malignant effusions. IL-1 and IL-2 were undetectable in malignant effusions, but elevated in both infective and tuberculous pericardial effusions. The levels of IL-1 and IL-2 were furthermore significantly higher in pericardial effusions due to infective compared to tuberculous causes. The concentration of IL-6, while elevated in all diagnostic classes, was significantly higher in the malignant group. Elevated levels of IL-10 and undetectable levels of IL-4 were observed in all three diagnostic groups. CONCLUSION: These findings suggest that tuberculous pericardial effusions arise due to a hypersensitivity reaction that is orchestrated by the TH-1 lymphocytes.     

Usefulness of pleural complement activation products in differentiating tuberculosis and malignant effusions.

OBJECTIVE: To determine whether measurement of the complement activation products SC5b-9 and C3a-desArg in pleural fluid can reliably differentiate tuberculous from malignant pleural effusions. DESIGN: Twenty-four patients with tuberculous pleuritis, 29 with malignant pleural effusion, and 30 control subjects with transudates were enrolled in the study. SCSb-9 and C3a-desArg were measured in pleural fluid using commercial ELISA tests, and their performances were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Patients with tuberculous pleuritis had higher mean levels of pleural SC5b-9 (5052 microg/L) and C3a-desArg (7436 microg/L) than those with malignant effusions (1048 and 2835 microg/L, respectively), whereas only SC5b-9 concentrations in the latter were comparable with controls. The area under the ROC curve (AUC) was 0.84 for SC5b-9 and 0.81 for C3a-desArg. Pleural SC5b-9 showed an accuracy of 80.8%, compared with 78.8% for C3a-desArg, when cut-off points of 1500 and 4500 microg/L, respectively, were used. Using a stepwise logistic regression model, the combination of pleural SCSb-9 > or =1500 microg/L, age < or =35 years, and pleural monocyte percentage > or =90% provided the highest accuracy for tuberculous pleurisy (88.5%, AUC 0.95). CONCLUSION: This pilot study suggests that pleural SC5b-9 is clinically useful for differentiating tuberculous and malignant pleural effusions.     

Differential diagnosis of tuberculous pleurisy by measurement of cytokine concentrations in pleural effusion

Study objective: Measurement of cytokine concentration in serum and pleural effusion may be useful in the differential diagnosis of tuberculous pleurisy.Patients and methods: We compared the biochemical properties and concentrations of cytokines in serum and pleural effusion samples of 18 patients with tuberculous pleurisy, 7 patients with parapneumonic pleurisy, and 25 patients with malignant pleurisy.Results: A high value of adenosine deaminase (ADA) was observed in pleural effusion of patients with tuberculosis. The serum concentrations of interleukin (IL)-1-beta, IL-2, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were similar among the three groups. However, the concentration of IFN-gamma in pleural effusion was high in tuberculous patients, and that of TNF-alpha was high in tuberculous and parapneumonic pleural fluid, but both cytokines were low in malignant pleural fluid. The sensitivity, specificity and accuracy of IFN-gamma in the diagnosis of tuberculous pleurisy were 94%, 100% and 98%, respectively. Similarly, those of TNF-alpha for the diagnosis of infectious pleurisy including tuberculous and parapneumonic pleurisy were 88%, 80% and 84%, respectively.Conclusions: Our results indicate that simultaneous measurement of IFN-gamma and TNF-alpha in pleural effusion is a useful diagnostic tool for differentiating tuberculous pleurisy from parapneumonic and malignant pleurisy.     

Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions

Background and aimsPrompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion).MethodsA retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups.ResultsPleural fluids with neutrophilic predominance and CRP levels > 45 mg/dL were most likely to be parapneumonic in origin (likelihood ratio = 7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP > 100 mg/L had the same performance characteristics (area under the curve = 0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75–80%) or specificity (97%), for complicated effusions.ConclusionPleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions.