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.