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Objective: To investigate the concentrations and clinical significance of interleukin (IL)-20 and IL-22 in pleural effusion with various etiologies., Methods: Pleural effusion (PE) and corresponding serum samples were obtained from 88 patients from Wuhan Tuberculosis Prevention and Control Institute from June 2011 to June 2013. There were 27 cases with malignant pleural effusion, 24 with tuberculous pleural effusion, 17 with bacterial pleural effusion and 20 with transudativeeffusion. The pleural and serum levels of IL-20 and IL-22 were determined by sandwich enzyme-linked immunosorbent assays (ELISA)., Results: (1) Except for transudativeeffusion, the concentration of IL-20 in malignant pleural effusion (36.8±5.1) ng/L, tuberculous pleural effusion (34.8±6) ng/L, bacterial pleural effusion (41.7±20.2) ng/L, were significantly higher than that of the corresponding serum concentration (29.7±5.97) ng/L, (27.3 ±6.7) ng/L, (25.6±4.7) ng/L (t=5.044, 3.804, 3.452, P<0.05). However, the concentration of IL-20 in pleural effusions of different causes showed no significant difference; malignant (36.8±5.1) ng/L, tuberculous(34.8±6.0) ng/L, bacterial (41.7±20.2) ng/L, transudate (34.1±7.3) ng/L (P>0.05). The concentration of IL-22 (median, quartiles) in tuberculouseffusion was 146.1 (39.8) ng/L and bacterial effusion 59.6 (484.3) ng/L was significantly higher than those in the corresponding serum concentrations 18.7 (9.8) ng/L, 15.7 (17.2) ng/L (Z value respectively -3.971, -3.290, P<0.05). The concentration of IL-22 in tuberculous pleural effusion, bacterial pleural effusion, transudative pleural effusion was significant higher than those in malignant pleural effusion respectively (all P<0.001). (2)The concentrations of IL-22 in malignant pleural effusion was correlated positively with those in serum (r=0.729, P<0.001). (3) With a cut-off value of 19.7 ng/L, pleural IL-22 exhibited a high sensitivity and specificity of 95.1% (39/41) and 88.9%(24/27) respectively, when used for distinguishing infectious pleural effusion (including tuberculous and bacterial effusion) from malignant pleural effusion (P<0.001)., Conclusions: Higher levels of IL-22 in tuberculous and bacterial pleural effusion were found when compared with corresponding serum levels and might be involved in the pathogenesis of infectious pleural effusion. Pleural IL-22 measurement provided reliable diagnostic efficiency for distinguishing infectious from malignant pleural effusion.

IL-17-producing CD8(+) T lymphocytes (Tc17 cells) have recently been detected in many cancers and autoimmune diseases. However, the possible implication of Tc17 cells in tuberculous pleural effusion remains unclarified. In this study, distribution and phenotypic features of Tc17 cells in both tuberculous pleural effusion (TPE) and peripheral blood from patients with tuberculosis were determined. The effects of proinflammatory cytokines and local accessory cells (pleural mesothelial cells) on Tc17 cell expansion were also explored. We found that TPE contained more Tc17 cells than the blood. Compared with IFN-γ-producing CD8(+) T cells, Tc17 cells displayed higher expression of chemokine receptors (CCRs) and lower expression of cytotoxic molecules. In particularly, Tc17 cells in TPE exhibited high expression levels of CCR6, which could migrate in response to CCL20. Furthermore, IL-1β, IL-6, IL-23, or their various combinations could promote Tc17 cell expansion from CD8(+) T cells, whereas the proliferative response of Tc17 cells to above cytokines was lower than that of Th17 cells. Pleural mesothelial cells (PMCs) were able to stimulate Tc17 cell expansion via cell contact in an IL-1β/IL-6/IL-23 independent fashion. Thus this study demonstrates that Tc17 cells marks a subset of non-cytotoxic, CCR6(+) CD8(+) T lymphocytes with low proliferative capacity. The overrepresentation of Tc17 cells in TPE may be due to Tc17 cell expansion stimulated by pleural proinflammatory cytokines and to recruitment of Tc17 cells from peripheral blood. Additionally, PMCs may promote the production of IL-17 by CD8(+) T cells at sites of TPE via cell-cell interactions.

Objective: The aim of this study was to investigate the distributions and relevance of Th1 and Th17 cells (IL-17-producing CD(+)(4) T cell), and the differentiation of Th17 cells in tuberculous pleural effusion., Methods: The percentages of both Th1 and Th17 cells in tuberculous pleural effusion and peripheral blood from 30 patients [male/female 12/18, age 16 - 63 years (average 41.2 year)] with tuberculous pleurisy were determined by flow cytometry, and comparison was made using Student's t test. The regulations of different combinations of IFN-γ, IL-1β, IL-6 and IL-12 on differentiation of Th17 cells were explored. Comparisons of the data between different groups were performed using Kruskal-Wallis one-way analysis of variance on ranks., Results: Both Th1 [(39 ± 11)% vs (8 ± 3)%; t = 17.37, P < 0.05] and Th17 cells [(2.8 ± 0.9)% vs (0.7 ± 0.3)%; t = 14.78, P < 0.05] were significantly increased in tuberculous pleural effusion compared with peripheral blood. The proportions of Th17 cells were correlated positively with those of Th1 cells both in tuberculous pleural effusion and in peripheral blood (r = 0.61, 0.49, respectively; both P < 0.05). IL-1β or IL-6 promoted the differentiation of Th17 cells, and their combination resulted in further increase of the differentiation of Th17 cells, while IFN-γ and IL-12 reduced the percentages of Th17 cells. Moreover, these two cytokines significantly impaired the promotive effect induced by IL-1β plus IL-6., Conclusion: This study showed that Th1/Th17 balance existed in tuberculous pleural effusion, and was mainly due to the generation and differentiation of Th17 cells induced by IL-1β and IL-6, but reversed by IFN-γ and IL-12 in tuberculous pleural effusion.

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.

Both T helper interleukin 17 (IL-17)-producing cells (Th17 cells) and regulatory T cells (Tregs) have been found to be increased in human tuberculous pleural effusion (TPE); however, the possible interaction between Th17 cells and Tregs in TPE remains to be elucidated. The objective of the present study was to investigate the distribution of Th17 cells in relation to Tregs, as well as the mechanism of Tregs in regulating generation and differentiation of Th17 cells in TPE. In the present study, the numbers of Th17 cells and Tregs in TPE and blood were determined by flow cytometry. The regulation and mechanism of CD39(+) Tregs on generation and differentiation of Th17 cells were explored. Our data demonstrated that the numbers of Th17 cells and CD39(+) Tregs were both increased in TPE compared with blood. Th17 cell numbers were correlated negatively with Tregs in TPE but not in blood. When naïve CD4(+) T cells were cultured with CD39(+) Tregs, Th17 cell numbers decreased as CD39(+) Treg numbers increased, and the addition of the anti-latency-associated peptide monoclonal antibody to the coculture reversed the inhibitory effect exerted by CD39(+) Tregs. This study shows that Th17/Treg imbalance exists in TPE and that pleural CD39(+) Tregs inhibit generation and differentiation of Th17 cells via a latency-associated peptide-dependent mechanism.