Malignant Pleurisy Research Articles

The diagnostic value and validation of IL-22 combimed with sCD40L in tuberculosis pleural effusion

BackgroundThere is substantial evidence indicating that cytokines play a role in the immune defense against tuberculosis. This study aims to evaluate the levels of various cytokines in pleural effusion to ditinguish between tuberculosis pleurisy and malignant pleurisy.MethodsA total of 82 participants with pleural effusion were included in the training cohort, and 76 participants were included in the validation cohort. The individuals were divided into tuberculosis and malignant pleurisy groups. The concentrations of interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, interferon-γ (IFN-γ), soluble CD40 ligand (sCD40L) and tumor necrosis factor-α (TNF-α) in pleural effusion were measured using a multiplex cytokine assay. The threshold values were calculated according to the receiver operating characteristic (ROC) curve analysis to aid in diagnosing tuberculosis pleurisy. Furthermore, the combined measure was validated in the validation cohort.ResultsThe levels of all 14 cytokines in pleural effusion were significantly higher in participants with tuberculosis compared to those with malignant pleurisy (all P < 0.05). The area under the curve (AUC) was ≥ 0.920 for the IL-22, sCD40L, IFN-γ, TNF-α and IL-31, which were significantly increased in tuberculous pleural effusion (TPE) compared to MPE in the training cohort. Threshold values of 95.80 pg/mL for IFN-γ, 41.80 pg/mL for IL-31, and 18.87 pg/mL for IL-22 provided ≥ 90% sensitivity and specificity in distinguishing between tuberculosis pleurisy and malignant pleurisy in the training cohort. Among these, IL-22 combined with sCD40L showed the best sensitivity and specificity (94.0% and 96.9%) for diagnosing tuberculosis pleurisy, and this finding was validated in the validation cohort.ConclusionWe demonstrated that the levels of IL-1β, IL-4, IL-6, IL-10, IL-17 A, IL-17 F, IL-21, IL-22, IL-25, IL-31, IL-33, IFN-γ, sCD40L and TNF-α in pleural effusion had significant difference between tuberculosis pleurisy and malignant pleurisy. Specifically, IL-22 ≥ 18.87 pg/mL and sCD40L ≥ 53.08 pg/mL can be clinically utilized as an efficient diagnostic strategy for distinguishing tuberculosis pleurisy from malignant pleurisy.

The levels of soluble CD137 are increased in tuberculosis patients and associated with disease severity and prognosis.

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p=0.012) and correlated with disease severity (p=0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p=0.018). Several blood cytokines, such as IL-6 (p=0.0147), IL-8 (p=0.0477), IP-10 (p ≤0.0001) and MCP-1 (p=0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p=0.002) and cytotoxic T cells (p=0.036) were significantly lower in SE patients than in non-SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p=0.0008) and cytotoxic T cells (p=0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p=0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis.

Histiocytic pleural effusion: the strong clue to malignancy

BackgroundThere have been many studies on the clinical characteristics of neutrophilic, lymphocytic, and/or eosinophilic pleural effusion. While caring for patients with pleural effusion, we found that histiocytic pleural effusion (HisPE) was not uncommon. However, few studies have explored HisPE. The purpose of the present study was to determine the clinical characteristics and etiologies of HisPE.MethodsIn this retrospective study, HisPE was defined as pleural fluid white blood cells comprised of ≥ 50% histiocytes. Using a clinical data warehouse, patients with HisPE among all patients aged >18 years who underwent thoracentesis and pleural fluid analysis between January 2010 and December 2019 at Ulsan University Hospital were enrolled. A total of 295 (9.0%) of 3279 patients who underwent thoracentesis were identified as HisPE patients. Among them, 201 with exudative HisPE were included. Clinical characteristics and etiologies were extracted from medical records and analyzed.ResultsAmong the 201 patients with exudative HisPE, the major causes were malignant pleural effusion (n = 102 [50.7%]), parapneumonic effusion (n = 9 [4.5%]), and tuberculous pleurisy (n = 9 [4.5%]). In the 102 patients with malignant pleural effusion, the main types of cancer were lung (n = 42 [41.2%]), breast (n = 16 [15.7%]), and stomach cancer (n = 11 [10.8%]). Among lung cancers, adenocarcinoma (n = 34 [81.0%]) was the most common histology.ConclusionsThe leading cause of exudative HisPE was malignancy, particularly lung cancer. Physicians should consider the possibility of malignant disease if histiocytes are predominantly present in pleural effusion.

Multifocal pleural capillary hemangioma: a rare cause of hemorrhagic pleural effusion-case report

BackgroundCapillary hemangioma can be found in many organs, but rarely in pleura. Previously, only localized pleural capillary hemangioma cases have been reported. Corticosteroids are the most commonly recommended drugs in capillary hemangioma.Case presentationHere, we present a case of a young woman with recurrent hemorrhagic pleural effusion. Despite repeatedly thoracentesis, the routine examinations, including chest computed tomography (CT) scan, pleural effusion biochemical test, and cytology all failed to make a definite diagnosis. Thus, single port video-assisted thoracoscopy (VATS) was then performed. Numerous nodules arising from the parietal pleura were found, and biopsies showed multifocal pleural capillary. However, recurrent pleural effusion was successfully managed by oral azathioprine, after failure of dexamethasone treatment.ConclusionsTo our knowledge, this is the first case of a patient with recurrent hemorrhagic pleural effusion masquerading as malignant pleurisy, but in fact caused by multifocal pleural capillary hemangioma.

Success rate of medical thoracoscopy and talc pleurodesis in malignant pleurisy: A single-centre experience.

Malignant pleurisy is associated with advanced oncological disease and dyspnoea is the most common presenting symptom. Pleurodesis is the preferred palliative and supportive treatment option, targeting symptom relief. The identification of clinical and endoscopic features that determine the success of talc pleurodesis in malignant pleurisy could guide clinical decision-making. All symptomatic patients with malignant pleurisy subjected to talc pleurodesis through medical thoracoscopy between January 2012 and December 2015 were included. Univariate and multivariate analyses were performed to identify factors associated with successful pleurodesis. Of the 155 patients, 122 (78%) were classified as having a successful pleurodesis based on clinical and radiological criteria. Factors associated with unsuccessful pleurodesis (univariate analysis) were the presence of pleural adhesions (odds ratio (OR): 0.43 (95% CI: 0.19-0.96); P = 0.04), extensive spread of pleural lesions (OR: 0.17 (95% CI: 0.05-0.59); P = 0.001), the use of systemic corticosteroids (OR: 0.28 (95% CI: 0.10-0.83); P = 0.02) and a prolonged time period between the clinical diagnosis of the pleural effusion and the moment of pleurodesis (OR: 0.14 (95% CI: 0.06-0.32); P < 0.0001). The latter being associated with failure of pleurodesis in a multivariate analysis (OR: 0.08 (95% CI: 0.01-0.25); P < 0.0001). Chest ultrasound prior to pleurodesis showed a sensitivity of 91% and a specificity of 88% in predicting the success of pleurodesis. The success rate of pleurodesis in malignant pleurisy could potentially be enhanced by correct patient selection and early referral for pleurodesis. Ultrasonic assessment of pleural adhesions and potential lung expansion prior to pleurodesis is useful in clinical decision-making.

False Negative Pleural Cytology in Patient with Malignant Pleurisies: Is Pleural EpCAM-Positive Microparticles a Complementary Tool for Diagnosis?

The diagnosis of neoplastic pleurisies remains difficult because of frequent false negative cytological analysis. Thoracoscopy remains the gold standard to distinguish benign from malignant pleural effusion, but it is invasive and not suitable for all patients. Microparticles (MPs) are promising potential biomarkers and could represent a new approach to identify patients with malignant pleural effusions. We have recently reported the presence of EpCAM-positive-MPs (EpCAM+MPs) in malignant pleurisies that could be routinely used as a complementary tool with cytology for the diagnosis of pleural malignancy. Here we describe three cases of pleural cancer patients negative for cancer cells but positive for EpCAM+MPs in the pleural fluid. This study confirmed the possibility to apply in clinical practice recent data about EpCAM+MPs, detected in pleural fluid, as a non-invasive pleural biomarker useful to increase sensitivity of cytology. In particular, we suggest in patients with a strong suspicion of pleural cancer to search pleural EpCAM+-MPs as a complementary diagnostic tool in case of negative cytological analysis of pleural fluid.

P2.01-042 T Cells Subsets with INF-Gamma, TNF-Alpha and ADA in Distinguishing Tuberculous from Malignant Pleural Effusions

The differential diagnosis of tuberculous and malignant pleural effusion (PE) is extremely difficult and continues to pose clinical challenges. We aimed to evaluate the utility of pleural fluid Interferon gamma (IFN- γ), Adenosine deaminase (ADA), Tumar necrosis factor-alpha (TNF-a) levels with T cells subsets in differential diagnosis of malignant (MPE) and tuberculous pleural effusions (TPE). Forty patients with pleural effusion (20 tuberculous and 20 malignant) were included in the study. The percentages of CD3 lymphocyte, CD4 lymphocyte and Treg (CD4 CD25) T cells in pleural effusion from patients with tuberculous and malignant pleurisy were determined by flow cytometry. The concentrations of TNF-a, IFN-γ and ADA were simultaneously determined in pleural fluids by enzyme linked immunosorbent assay and colorimetric method. The ADA activity, TNF-a and IFN-g concentration were significantly higher in tuberculous than MPE (84.22±41.47 vs. 23.19±17.93 U/l : P<0.0001, 122.45±47.69 vs. 35.03±31.88 pg/ml : P < 0.0001 and 2.26±1.62 vs. 0.3±0.20 IU/ml : P<0.0001 respectively ). T-cells subsets (CD3 T-cells, CD4 T-cells and T reg cells) were significantly higher in TPE than MPE (76.46% vs. 65.29%; P 0.004, 51.21% vs. 43.50%; P 0.044 and 14.60% vs. 12.43%; P 0.032 respectively). CD3 plus CD4 as well as CD3 plus CD4 plus T reg combinations were all 100% specific for discriminating TPE from MPE. TNF-α plus IFN-γ, TNF-α plus ADA, as well as TNF-α plus IFN-γ plus ADA, were 100% specific for discriminating TPE from MPE. Furthermore, the specificity of combined-diagnostic value of TNF-α, IFN-γ, ADA with T cells subsets was > 95 %. The combinations of pleural fluid IFN-γ, ADA, TNF-a levels and T cells subsets could effectively address the challenge of distinguishing tuberculous pleural effusion from malignant pleural effusion.

Concomitant Interstitial Lung Disease Is a Risk Factor for Pleural Invasion in Lung Cancer

Lung carcinoma is often associated with interstitial lung disease (ILD), and the prognosis of lung cancer accompanied by ILD is unfavorable. In this study, cases of patients with primary lung cancer with or without ILD were reviewed to analyze surgical outcome, with special interest in the conformity of clinical and pathologic stages, pathologic findings of pleural invasion, malignant pleurisy first detected at the time of thoracotomy, and survival. Retrospective chart review was performed for 1,264 primary lung cancer patients who underwent surgery from 2004 to 2015. Concomitant ILD was diagnosed by pathological examination or preoperative chest computed tomography findings. ILD was found in 104 patients (8.2%) with primary lung cancer. Conformity of clinical and pathological stages in the ILD-positive patients was poor, with a lower kappa value than that for the 1,160 ILD-negative patients (0.34 versus 0.51). The ILD group had significantly higher incidences of pleural invasion and unexpected malignant pleurisy than did the non-ILD group (for pleural invasion, 49.0% versus 24.5%, p < 0.0001; for malignant pleurisy, 7.69% versus 1.47%, p < 0.0001). The 5-year overall survival rates of the ILD group showed significantly lower than those of the non-ILD group (45.2% versus 70.1%; p= 0.0014) after propensity score matching. In lung cancer, the concomitant existence of ILD is a risk factor for pleural invasion. Concomitant ILD might cause underestimation of clinical staging, increase the chance of unexpected malignant pleurisy during surgery, and shorten survival time.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Are soluble IL-2 receptor and IL-12p40 levels useful markers for diagnosis of tuberculous pleurisy?

Background: The differential diagnostic utilities of the levels of soluble interleukin (IL)-12p40 and the IL-2 receptor in sera and pleural effusions were evaluated in patients with exudative pleural effusions. Methods: We enrolled a total of 120 patients with exudative pleural effusions. The clinical, radiological, and histopathological diagnoses were tuberculous pleurisy in 52, malignant pleurisy in 39, and parapneumonic effusions in 29 patients. Results: We measured serum IL-12p40 and adenosine deaminase (ADA) levels in patients with tuberculous pleurisy and in a control group treated for pleural effusion to determine if such levels were useful in the diagnosis of pleural effusion (p < 0.005). Definite microbiological or histopathological diagnoses of tuberculous pleurisy or pleural effusion were recorded, and we found that ADA and serum soluble IL-2 receptor levels aided in diagnosis (p < 0.001). The levels of ADA and soluble IL-2 in pleural effusions afforded sensitivities and specificities of 84.62% and 82.69% and of 70.59% and 80.88%, respectively. The soluble IL-2 receptor level afforded a sensitivity and specificity of 82.69% and 52.9%. IL-12p40 levels in pleural effusions and sera afforded sensitivities and specificities of 80.77% and 80.77% and of 60.29% and 39.71%, respectively. Conclusion: Soluble IL-2 receptor levels in patients with tuberculous pleurisy serve as markers of disease in non-endemic countries, similarly to ADA levels.

Systemic Taxotere Chemotherapy for Metastatic Tumor Pleurisy in Cats with Spontaneous Breast Cancer

Systemic and intrapleural chemotherapy for metastatic tumor pleurisy was carried out in cats with breast carcinoma. The animals (n=18) were divided into 2 groups. Cats of the systemic chemotherapy group received 3-6 courses of taxotere (30 mg/m(2); n=7) or 3 courses of taxotere (20 mg/m(2)) in combination with doxorubicin (20 mg/m(2)at 21-day intervals (n=5) during the adjuvant period of therapy for metastatic tumor pleurisy. Objective effect was attained in 10 (84.6%) cats: partial remission in 3 (25%) and complete remission in 7 (58.3%, p>0.05) cats. Metastatic pleurisy progressed in 2 (16.7%) cats. The median time to progression reached 1.79 months, median lifespan 2.8 months. The animals of intrapleural chemotherapy group (n=6) received 1-4 courses of cyclophosphamide (250 mg/m(2)) at 1-week interval during the adjuvant period without therapy for malignant pleurisy. Malignant pleurisy progressed in all cats. The median time to progression was equal to median lifespan (0.6 months). The therapy for malignant pleurisy in cats with breast cancer is regarded as the second-line chemotherapy with taxotere preferable as a monotherapy or in combination with doxorubicin.

Differential diagnosis of tuberculous and malignant pleurisy using pleural fluid adenosine deaminase and interferon gamma in Taiwan

Accurately differentiating tuberculous pleurisy from lung cancer is important for disease management but difficult using conventional laboratory methods. This study assessed the value of adenosine deaminase (ADA) and interferon gamma (IFN-γ) for differentiating the two conditions in a region of Taiwan with a high prevalence of tuberculosis. The study population comprised patients with lymphocytic exudative pleural effusions: tuberculous (n=24) and malignant (n=42). Mean levels of ADA and IFN-γ in pleural fluid, measured with commercial standardized kits, were significantly higher for tuberculous than for malignant pleurisy (p<0.001 for both). For differentiating the two effusions, results for ADA versus IFN-γ were: sensitivity, 70.8% versus 91.7%; specificity, 95.2% versus 97.6%; positive predictive value, 89.5% versus 96.7%; and negative predictive value, 85.1% versus 95.3%. IFN-γ allows precise diagnosis of pleural tuberculosis, but ADA is easier to use, has a low cost, and results are quickly available. Our study confirms previous studies and extends the usefulness of these diagnostic methods to a wider group of clinical laboratories by showing the reliability of standardized relatively inexpensive commercial kits. We recommend that initial ADA screening be used in conjunction with IFN-γ measurements for differential diagnosis of tuberculous pleurisy.

Diagnostic value of neurotrophin expression in malignant pleural effusions

Neurotrophins (NTs) modulate the growth of human malignancies, including lung cancers. Our prospective study evaluated the accuracy of pleural NTs [nerve growth factor, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (nT3) and 4 (nT4)] levels for differentiating benign from malignant pleural exudates. Levels of NTs were measured by ELISA in 170 patients with non-neutrophilic (<50%) exudative benign or malignant pleurisies diagnosed by pleuroscopy. Fifty-nine benign (9 infections and 50 inflammatory diseases) and 111 malignant (50 extrathoracic tumors, 51 lung cancers and 10 mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Levels of BDNF were significantly higher in malignant than in benign effusions [17 pg/ml (0-367) vs. 8 pg/ml (0-51), p<0.05]. ROC analysis showed an area under the curve of 0.609 (p=0.012; best threshold 44 pg/ml). Pleural BDNF levels were significantly higher in pleural metastasis of pulmonary tumors and in mesothelioma than in pleural benign effusions. Finally, a higher proportion of pleural nT3 was detected in squamous cell lung carcinoma in comparison to that in non-squamous cell lung carcinoma (72.7 vs. 10%, p<0.0001). NTs and particularly BDNF may play a role in the pathogenesis of malignant pleural effusions.

Differential Levels of Cytokines and Soluble Fas Ligand between Tuberculous and Malignant Effusions

Tuberculous pleurisy, which is characterized by an extensive inflammatory exudate in the pleural space, is a common manifestation of extrapulmonary tuberculosis caused by Mycobacterium tuberculosis infection but is difficult to diagnose. This study compared concentrations of three cytokines (interferon-γ and interleukin [IL]-2 and -4) and soluble Fas ligand in serum and pleural effusions from 36 patients with tuberculous pleurisy, 30 with malignant pleurisy and 30 healthy volunteers. Interferon-γ concentration was significantly higher in serum and pleural effusions, and the concentration of soluble Fas ligand was significantly higher in pleural effusion, from patients with tuberculous pleurisy than in those with malignant pleurisy. Levels of IL-2 and IL-4 were also raised in serum, but failed to reach statistical significance. Interferon-γ and soluble Fas ligand levels were significantly higher in pleural effusion than in serum. Pleural soluble Fas ligand concentrations correlated linearly with those of interferon-γ in patients with tuberculous pleurisy. These findings suggest a predominant T-helper-1 response to M. tuberculosis infection.

Malignant Pleurisy Associated with Primary Lung Cancer Well Controlled by Pleurodesis Using Distilled Water

The patient was an 84-year-old man patient diagnosed as malignant pleurisy associated with lung cancer. After drainage of the right pleural effusion, pleurodesis with distilled water was performed. Despite the enlargement of the primary lesion of the lung cancer during the follow-up period, the amount of pleural effusion did not increase for more than one year. No adverse effects associated with pleurodesis were noted. Pleurodesis with distilled water should be considered as one of the choices for treatment in the management of malignant pleurisy especially in elderly.

Prognostic value of metabolic imaging in non-small cell lung cancers with neoplasic pleural effusion

The intensity of the [F]fluorodeoxyglucose (F-FDG) uptake is an independent prognostic indicator in non-small cell lung cancer (NSCLC). We evaluate the relationship between the metabolic activity of the primary and the pleurisy in T4 NSCLC. 25 patients (16 males, nine females, mean age 63 years, performance status 1) with pathology-proven, T4 NSCLC and malignant pleurisy were included. All were treated by a platinum salt-based chemotherapy regimen. Positron emission tomography (F-FDG-PET) was performed before treatment, according to a routine procedure. Regions of interest were placed over the primary and the pleural effusion on the transaxial slice showing the highest activity. The maximum pixel standard uptake values (SUVs) were calculated. Overall survival was determined by standard Kaplan-Meier survival analysis. All patients were followed up until death. The median survival for the entire population was 83 days (7-988). The SUVs were higher in the primary than in the pleurisy (9.2+/-5.6 and 5.5+/-2.2, respectively). There was no correlation between primary and pleurisy SUVs (r=0.3, P>0.05). The metabolic activity of the primary tumor did not predict the outcome: the median survival was 77.5 days (range 7-988) and 87 days (19-454) in the groups with SUVs lower and higher than the median value (8.7), respectively (P>0.05). By contrast, the metabolic activity of the pleurisy was significantly correlated with the median survival, which was 196 days (40-988) when the SUVs were lower than the median value (5) and 74 days (7-170) when they were higher (P=0.0096). Among patients with T4 NSCLC, those with high metabolic activity in the pleural effusion have a dire prognosis, whereas the metabolic activity of the primary fails to predict the survival.

Diagnostic value of interleukine-6, transforming growth factor-beta 1 and vascular endothelial growth factor in malignant pleural effusions

We evaluate the accuracy of pleural interleukine-6 (IL-6), transforming growth factor-beta 1 (TGF-beta1), and vascular endothelial growth factor (VEGF) levels for differentiating benign from malignant pleural exudates. Levels of IL-6, TGF-beta1, and VEGF were measured by ELISA in 103 patients with non neutrophilic (<50%) exudative pleurisy including both benign and malignant effusions. Pleurisies were split into benign and malignant according to the pathological diagnosis. Thirty-nine benign (seven infections; 32 inflammatory diseases) and 64 malignant (34 extrathoracic tumors; 25 lung cancers; five mesotheliomas) pleural exudates were diagnosed by thoracoscopy. Pleural reticulo-monocyte count, protein Light's ratio and lactic dehydrogenase Light's ratio were significantly higher in malignant than in benign effusions (p<0.05, p<0.001 and p<0.001, respectively). The median (range) level of VEGF was significantly higher in malignant than in benign effusions (664.50 pg/ml [10-40,143] vs 349 pg/ml [10-8888]) (p<0.05). VEGF levels correlated with pleural LDH (r=0.41, p<0.0001), glucose (r=-0.30, p<0.01) and red cell count (r=0.57, p<0.0001). No significant difference was found between malignant and benign effusions with respect to IL-6 (26.8 ng/ml [1.8-421] vs 18.4 ng/ml [0.45-400], respectively) and TGF-beta1 (1079 pg/ml [18-6206] vs 1123 pg/ml [34-5447]) levels. ROC analysis between benign and malignant pleurisies for VEGF showed an area under the curve of 619 (p=0.03) with a value of 382 pg/ml as the best threshold for distinguishing benign from malignant effusions. Malignant effusions may enhance the release of VEGF in pleural space and its measurement may help in the diagnosis of malignant effusion.

Increased Pleural Soluble Fas Ligand (sFasL) Levels in Tuberculosis Pleurisy and Its Relation with T-helper Type 1 Cytokines

Tuberculosis (TB) pleurisy is accepted to be the best model for evaluating the local protective cellular immune response to Mycobacterium tuberculosis (MTB) since it can be spontaneously self-cured. Therefore, we aimed to evaluate the involvement of cytokines and the soluble apoptosis-modulating factors sFas and sFasL in local protective cellular immunity to MTB. Pleural fluid samples were collected from 35 patients with TB pleurisy, 39 patients with malignant pleurisy, and 14 patients with non-TB nonmalignant (n-TB n-M) pleurisy and were evaluated for the levels of several cytokines, soluble Fas (sFas), and sFas ligand (sFasL) by using ELISA. The levels of IFN-gamma, IL-12p40, IL-18, IL-8, and sFasL in TB pleurisy were significantly higher in comparison to those in the malignant pleurisy and n-TB n-M pleurisy groups. In addition, pleural sFasL levels were increased and positively correlated with IFN-gamma and IL-18 levels in TB patients. In conclusion, this study demonstrates that Th1-type-specific cellular immunity is responsible for protective immunity in TB and suggests that Fas-mediated apoptosis may be at least a part of protective immunity to tuberculosis and could be regulated by type 1 T-cell response. IFN-gamma and sFasL levels can be used as diagnostic markers for differing TB pleurisy from other pleurisies.

IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2.

The levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1 beta was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.

Differential cytokine levels and immunoreactivities against Mycobacterium tuberculosis antigens between tuberculous and malignant effusions

Much effort has been devoted to the identification of immunologically important factors in tuberculous pleurisy (TBP) and malignant pleurisy (MP) to improve the differential diagnosis of the two major causes of lymphocyte-dominant pleurisy. This study evaluated the immunoreactivity and potential diagnostic utility of both host (cytokines and chemokines) and pathogen (mycobacterial proteins) factors in pleural effusions. Effusion samples were collected from 41 patients with MP caused by lung cancer and from 81 patients with TBP. The concentrations of nine cytokines and chemokines (interleukin (IL)-12 p40, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-6, IL-10, CXCL8/IL-8, CXCL10/IP-10, CCL3/MIP-1alpha, and CCL4/MIP-1beta) and antibody responses (IgG, IgM, and IgA) against five Mycobacterium tuberculosis antigens (early secreted antigenic target (ESAT)-6, 30-kDa, MTB12, 38-kDa, and a heparin-binding hemagglutinin (HBHA)) were determined in pleural fluids using enzyme-linked immunosorbent assays (ELISA). In the logistic regression, IFN-gamma (odds ratio, 7.178; 95% confidence interval (CI), 2.258-22.817; p=0.001), IL-12 p40 (odds ratio, 11.037; 95% CI, 3.38-36.037; p<0.001), and IL-6 (odds ratio, 3.295; 95% CI, 1.147-9.463; p=0.027) were found to be statistically significant cytokines predicting tuberculous from malignant effusions. Although IgG responses to all of the M. tuberculosis antigens tested were significantly higher in effusions from TBP (p<0.001) compared with those from MP, the logistic regression showed IgG levels for ESAT-6 and MTB12 to be statistically significant for differentiation of TBP from MP. HBHA showed the highest sensitivity of IgM antibody responses in TBP in comparison with other antigens. These data indicate that selected mycobacterial antigens (ESAT-6 and MTB12) and cytokine markers (IFN-gamma, IL-12p40, and IL-6) provide useful information for differentiating tuberculous and malignant effusions in clinical practice.