title: Proinflammatory cytokines, transforming growth factor-beta1, and fibrinolytic enzymes in loculated and free-flowing pleural exudates.
abstract: OBJECTIVE
  To measure tumor necrosis factor (TNF) alpha, interleukin (IL) 1beta, and transforming growth factor (TGF) beta1 in loculated and free-flowing pleural effusions caused by malignancy, tuberculosis (TB), and pneumonia and their relationship with plasminogen activator inhibitor-type 1 (PAI-1) and tissue-type plasminogen activator (tPA) and to compare the differences between loculated and free-flowing effusions.
  
  
  METHODS
  A prospective study.
  
  
  METHODS
  The effusion levels of TNF-alpha, IL-1beta, TGF-beta1, PAI-1, and tPA were measured in 29 patients with malignant effusions, 19 patients with TB, and 30 patients with parapneumonic effusions. Pleural effusions were divided into loculated and free-flowing groups by imaging studies. A group of 42 patients with loculated effusions was subdivided into primary and secondary loculation groups by chest ultrasonography.
  
  
  RESULTS
  The median levels of TNF-alpha (87.0 pg/mL), IL-1beta (13.8 pg/mL), TGF-beta1 (10,952.9 pg/mL), PAI-1 (111.2 ng/mL), and lactate dehydrogenase (LDH) [498 IU/dL] in the loculated group were significantly higher than those in the free-flowing group (TNF-alpha, 15.0 pg/mL; IL-1beta, 2.9 pg/mL; TGF-beta1, 6,117.3 pg/mL; PAI-1, 61.5 ng/mL, and LDH, 266 IU/dL). In both the loculated and free-flowing effusions, the levels of TGF-beta1 correlated positively with those of TNF-alpha (r = 0.51 and p < 0.001 vs r = 0.42 and p < 0.05, respectively) and IL-1beta (r = 0.52 and p < 0.001 vs r = 0.49 and p < 0.01, respectively), and the values of PAI-1 correlated positively with those of TNF-alpha (r = 0.59 and p < 0.001 vs r = 0.55 and p < 0.001, respectively), IL-1beta (r = 0.35 and p < 0.05 vs r = 0.47 and p < 0.01, respectively), and TGF-beta1 (r = 0.53 and p < 0.001 vs r = 0.58 and p < 0.001, respectively). In contrast, the levels of tPA correlated negatively with those of TNF-alpha (r = -0.37, p < 0.05) and IL-1beta (r =-0.56, p < 0.001) in loculated effusions. Twenty-seven of 42 patients with loculated effusions were classified into a secondary loculation group, which, compared with the primary loculation group, had significantly higher median levels of effusion TNF-alpha (119.2 vs 14.2 pg/mL, respectively; p = 0.001), IL-1beta (33.3 vs 3.4 pg/mL, respectively; p < 0.001), TGF-beta1 (13,152.7 vs 7746.0 pg/mL, respectively; p = 0.041), and PAI-1 (114.9 vs 94.1 pg/mL, respectively; p = 0.019).
  
  
  CONCLUSIONS
  Compared with free-flowing effusions, fibrinolytic activity was depressed in loculated effusions. A higher intensity of pleural inflammation in loculated effusions may enhance the release of TNF-alpha, IL-1beta, and TGF-beta1, which may subsequently increase the levels of PAI-1. The imbalance of PAI-1 and tPA in pleural spaces may lead to fibrin deposition and loculation of pleural effusions.
authors.affiliation: Department of Chest Medicine, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Chung
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Chen
authors.forename: Joen-Rong
authors.initials: JR
authors.lastname: Sheu
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Chen
authors.forename: Shi-Chuan
authors.initials: SC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005122:Exudates and Transudates / Q000737:chemistry*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D010996:Pleural Effusion / Q000737:chemistry*; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis*; D053773:Transforming Growth Factor beta1; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D007375:Interleukin-1; D017395:Plasminogen Activator Inhibitor 1; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D010959:Tissue Plasminogen Activator