Clinical Value of Tumor Markers for Determining Cause of Pleural Effusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It is often challenging to distinguish tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE); thoracoscopy is among the techniques with the highest diagnostic ability in this regard. However, such invasive examinations cannot be performed on the elderly, or on those in poor physical condition. The aim of this study was to explore the differential diagnostic value of carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) associated antigen in patients with TPE and MPE.</p><p><b>METHODS</b>Using electrochemiluminescence, we measured the concentration of tumor markers (TMs) in the pleural effusion and serum of patients with TPE (n = 35) and MPE (n = 95). We used receiver operating characteristic (ROC) curve analysis to evaluate the TMs and differentiate between TPE and MPE.</p><p><b>RESULTS</b>The cut-off values for each TM in serum were: CA125, 151.55 U/ml; CA199, 9.88 U/ml; CEA, 3.50 ng/ml; NSE, 13.27 ng/ml; and SCC, 0.85 ng/ml. Those in pleural fluid were: CA125, 644.30 U/ml; CA199, 12.08 U/ml; CEA, 3.35 ng/ml; NSE, 9.71 ng/ml; and SCC, 1.35 ng/ml. The cut-off values for the ratio of pleural fluid concentration to serum concentration (P/S ratio) of each TM were: CA125, 5.93; CA199, 0.80; CEA, 1.47; NSE, 0.76; and SCC, 0.90. The P/S ratio showed the highest specificity in the case of CEA (97.14%). ROC curve analysis revealed that, for all TMs, the area under the curve in pleural fluid (0.95) was significantly different from that in serum (0.85; P < 0.001).</p><p><b>CONCLUSIONS</b>TMs in TPE differ significantly from those in MPE, especially when detected in pleural fluid. The combined detection of TMs can improve diagnostic sensitivity.</p>

Incidence of pleural effusion in patients with pulmonary embolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>No data on the incidence of pleural effusion (PE) in Chinese patients with pulmonary embolism are available to date. The aim of the current study was to investigate the frequency of PE in a Chinese population of patients with pulmonary embolism.</p><p><b>METHODS</b>This was a retrospective observational single-center study. All data of computed tomography pulmonary angiography (CTPA) performed over 6-year period on adult patients with clinically suspected pulmonary embolism were analyzed.</p><p><b>RESULTS</b>From January 2008 until December 2013, PE was identified in 423 of 3141 patients (13.5%) with clinically suspected pulmonary embolism who underwent CTPA. The incidence of PE in patients with pulmonary embolism (19.9%) was significantly higher than in those without embolism (9.4%) (P < 0.001). Majority of PEs in pulmonary embolism patients were small to moderate and were unilateral. The locations of emboli and the numbers of arteries involved, CT pulmonary obstruction index, and parenchymal abnormalities at CT were not associated with the development of PE.</p><p><b>CONCLUSIONS</b>PEs are present in about one fifth of a Chinese population of patients with pulmonary embolism, which are usually small, unilateral, and unsuitable for diagnostic thoracentesis.</p>

Immune Regulation of Interleukin-27 in Malignant Pleural Effusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE.</p><p><b>METHODS</b>The distribution of IL-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions of cytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription (STAT) signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored.</p><p><b>RESULTS</b>The expression of IL-27 was increased in MPE when compared with blood (147.3 ± 25.1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04). IL-27 was noted to suppress both proliferation (18.33 ± 0.21 vs. 27.77 ± 0.88, P = 0.0005) and migration (1.82 ± 0.44 vs. 3.13 ± 0.07, P = 0.04) of A549 cells, but obviously promoted apoptosis of A549 cells (9.47 ± 1.14 vs. 4.96 ± 0.17, P = 0.02) by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities of A549 cells to pleural mesothelial cell monolayer by activating different STAT signalings.</p><p><b>CONCLUSIONS</b>IL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.</p>

Combined detections of interleukin 27, interferon-γ, and adenosine deaminase in pleural effusion for diagnosis of tuberculous pleurisy / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies reported interleukin-27 (IL-27), interferon-γ (IFN-γ), or adenosine deaminase (ADA) alone plays a helpful role in diagnosing tuberculous pleural effusion (TPE). The present study aims at comparing the diagnostic accuracy of pleural IL-27, IFN-γ, and ADA, and investigate the diagnostic accuracy of the combination of IL-27, IFN-γ, or/and ADA for differentiating TPE from pleural effusions with the other etiologies.</p><p><b>METHODS</b>The concentrations of IL-27, IFN-γ and ADA were simultaneously determined in pleural fluids and sera from 40 patients with TPE; 26 with malignant pleural effusion, seven with infectious pleural effusion, and eight with transudative pleural effusion by enzyme linked immunosorbent assay and colorimetric method. The corresponding biochemical indexs were also simultaneously determined.</p><p><b>RESULTS</b>The concentrations of pleural IL-27 and IFN-γ in the tuberculous group were significantly higher than those in the malignant, infectious, and transudative groups. The concentrations of ADA in TPE were significantly higher than those in MPE or transudative effusions, while much lower than those in infectious effusions. Among these three biomarkers, IL-27 was the most effective for TPE diagnosis, with the cut off value of 900.8 ng/L. IL-27 had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis of TPE from non-TPEs. Combinations of IL-27, IFN-γ and ADA measurements further increased the sensitivity or specificity up to 100%.</p><p><b>CONCLUSIONS</b>Compared to non-TPEs, IL-27, IFN-γ and ADA all simultaneously increased in TPE; and among these three rapid detection methods, IL-27 appeared to be the best for distinguishing tuberculous from non-TPEs, especially from MPE. Combinations of the three markers (IL-27, IFN-γ and ADA) yielded the highest sensitivity and specificity. These findings suggest that the applications of a new biomarker, IL-27, alone or with IFN-γ and ADA, may contribute to more efficient diagnosis strategies in the management of tuberculous pleurisy.</p>

Cellular sources of interleukin 16 in benign and malignant pleural effusions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Interleukin 16 (IL-16) can be detected by ELISA in pleural effusion (PE) and its concentration is higher than in serum. This study investigated the cellular sources of IL-16 in PE.</p><p><b>METHODS</b>The samples of PE were collected from 34 patients who were newly diagnosed having PE in the pleural cavity. We performed cell culture to purify the pleural mesothelial cells (PMC), Wright staining to count the purity and immunocytochemical stain to identify the cultured cells. The intracellular IL-16 expression was detected by flow cytometry (FCM). The different cells in PE were first separated by magnetic cell sorting (MCAS) then the separated cells were cultured in RPMI1640 with 10% fetal calf serum (FCS). We extracted the supernatant and detected IL-16 concentration by ELISA. The IL-16 protein was detected by immunohistochemistry and double immunofluorescence staining.</p><p><b>RESULTS</b>The percentages of cells which secreted IL-16 were: CD3(+)CD8(-) cells ((74.27 ± 15.56)%, n = 34); CD3(+)CD8(+) cells ((69.86 ± 18.55)%, n = 34); CD19(+) cells ((45.30 ± 18.77)%, n = 15); CD14(+) cells ((16.91 ± 16.69)%, n = 15); and PMC ((2.05 ± 1.85)%, n = 7). The concentrations of IL-16 in the supernatant from cultured cells were: CD4(+) cells ((102.50 ± 42.51) ng/L, n = 5); CD8(+) cells ((92.58 ± 18.34) ng/L, n = 5); CD19(+) cells ((79.85 ± 5.62) ng/L, n = 5); CD14(+) cells ((58.51 ± 25.38) ng/L, n = 5); and PMC ((18.14 ± 8.37) ng/L, n = 5). In lymphocytes, monocytes/macrophages and PMC, we could observe the cells that expressed IL-16 protein. In paraffin-embedded sections, we also could observe by immunohistochemistry the CD4(+)IL-16(+) cells, CD8(+)IL-16(+) cells, CD19(+)IL-16(+) cells, and CD14(+)IL-16(+) cells.</p><p><b>CONCLUSIONS</b>IL-16 in PE is mainly secreted by T lymphocytes, including CD3(+)CD8(-) cells and CD3(+)CD8(+) cells. CD19(+) cells and CD14(+) cells can also secrete IL-16, but the percentage of PMC that can secrete IL-16 is very low.</p>

Effects of the TREM-1 pathway modulation during empyema in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The activation of triggering receptor expressed on myeloid cells-1 (TREM-1) in the presence of microbial components amplifies the inflammatory response. The aim of the present study was to investigate the effect of the modulation of the TREM-1 pathway during empyema in rats.</p><p><b>METHODS</b>Adult male Wistar rats were subjected to empyema induced by intrapleural injection of Pseudomonas aeruginosa and Staphylococcus aureus. The animals were treated with LP17 (a synthetic TREM-1 inhibitor), a control peptide, or a vehicle (normal saline). Differential cell count, flow cytometry and histological examination were performed to evaluate local inflammatory alterations. Concentrations of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in both pleural effusion and serum were measured by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>Although differential counts of each type of leukocytes in pleural effusion were not affected by LP17, a marked reduction in neutrophil numbers was seen in LP17 treated rats due to the reduction of both pleural effusion volume and total cell numbers. LP17 administration impaired concentration elevation in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in both pleural effusion and serum. It was found that survival rate in LP17 treated rats was much higher than that in control rats.</p><p><b>CONCLUSION</b>The modulation of the TREM-1 pathway by the use of LP17 appears to be beneficial during empyema in rats in attenuating pleural and systemic inflammatory responses.</p>

CD4+CD25+ regulatory T lymphocytes in tuberculous pleural effusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Active suppression by CD4+CD25+ regulatory T lymphocytes plays an important role in the down-regulation of T cell responses to foreign and self-antigens. This study was conducted to analyze whether the CD4+CD25+ regulatory T cells exist and function normally in tuberculous pleural effusion.</p><p><b>METHODS</b>The percentages of CD4+CD25+ T cells in pleural effusion and peripheral blood from patients with tuberculous pleurisy and peripheral blood from healthy control subjects were determined by flow cytometry. The expression of forkhead transcription factor Foxp3 was also examined. CD4+CD25+ and CD4+CD25(-) T cells from pleural effusion and blood were isolated, and were cultured to observe the effects of CD4+CD25+ T cells on proliferation response of CD4+CD25(-) T cells in vitro.</p><p><b>RESULTS</b>There were increased numbers of CD4+CD25+ T cells in tuberculous pleural effusion compared with peripheral blood from both patients with tuberculous pleurisy and normal subjects, and these cells demonstrated a constitutive high-level expression of Foxp3. Moreover, CD4+CD25+ T cells mediated potent inhibition of proliferation response of CD4+CD25(-) T cells.</p><p><b>CONCLUSION</b>The increased CD4+CD25+ T cells in tuberculous pleural effusion express a high level of Foxp3 transcription factor, while potently suppressing the proliferation of CD4+CD25(-) T cells.</p>

Expression of soluble triggering receptor expression on myeloid cells-1 in pleural effusion / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Triggering receptors expressed on myeloid cells (TREM) proteins are a family of cell surface receptors expressed broadly by cells of the myeloid lineage. The aim of this study was to investigate the clinical significance of soluble TREM-1 (sTREM-1) in pleural effusions, and to determine the effects of pneumonia on pleural sTREM-1 concentrations.</p><p><b>METHODS</b>Pleural fluid was collected from 109 patients who presented to the respiratory institute (35 with malignant pleural effusion, 31 with tuberculous pleural effusion, 21 with bacterial pleural effusion, and 22 with transudate). The concentrations of sTREM-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were determined in effusion and serum samples by enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The concentrations of sTREM-1 in bacterial pleural effusion were significantly higher than those in malignant, tuberculous, and transudative groups (all P < 0.001). An sTREM-1 cutoff value of 768.1 ng/L had a sensitivity of 86% and a specificity of 93%. Pleural sTREM-1 levels were positively correlated with levels of TNF-alpha and IL-1beta. Patients with complicating bacterial pneumonia did not have elevated concentration of sTREM-1 in pleural effusion when compared with patients without pneumonia.</p><p><b>CONCLUSIONS</b>Determination of pleural sTREM-1 may improve the ability of clinicians to differentiate pleural effusion patients of bacterial origin from those with other etiologies. The occurrence of bacterial pneumonia did not affect pleural sTREM-1 concentrations.</p>

Effects of antigen presentation of eosinophils on lung Th1/Th2 imbalance / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Antigen-loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2-type cytokine production in the draining lymph nodes. The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues.</p><p><b>METHODS</b>Airway EOSs were recovered from ovalbumin-sensitized and -challenged BALB/c mice, these EOSs were then cocultured with CD4+ cells isolated from sensitized mice in the absence or presence of anti-CD80 or/and -CD86 monoclonal antibodies. Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture. Cell-free culture supernatants were collected for detection of cytokines.</p><p><b>RESULTS</b>Airway EOSs functioned as CD80- and CD86-dependent antigen-presenting cells to stimulate lung CD4+ lymphocytes to produce interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma in in vitro assay. When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin-4, interleukin-5 and interleukin-13, but not interferon-gamma, production during the in vitro culture that was also CD80- and CD86-dependent.</p><p><b>CONCLUSION</b>EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen-presenting cells to promote expansion of Th2 cells in the lungs.</p>