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(Chest. 1999;116:1292-1296.)
© 1999 American College of Chest Physicians

Proinflammatory Cytokines and Fibrinolytic Enzymes in Tuberculous and Malignant Pleural Effusions*

Chung-Ching Hua, MD; Liang-Che Chang, MD; Yi-Chu Chen, BS and Shi-Chuan Chang, MD, PhD, FCCP

* From the Departments of Internal Medicine (Dr. Chung-Ching Hua) and Pathology (Dr. Liang-Che Chang), Chang Gung Memorial Hospital, Keelung; the Chest Department (Ms. Yi-Chu Chen and Dr. Shi-Chuan Chang), Veterans General Hospital-Taipei, and the School of Medicine (Dr. Shi-Chuan Chang), National Yang-Ming University, Taipei, Taiwan, ROC.

Correspondence to: Shi-Chuan Chang, MD, PhD, FCCP, Chest Department, Veterans General Hospital-Taipei, #201, Section 2, Shih-Pai Rd, Taipei, Taiwan 11217, ROC


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: To measure tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1ß (IL-1ß) 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-1ß, 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-1ß. In malignant pleural fluid, positive correlations were found between the values of proinflammatory cytokines (TNF-{alpha} and IL-1ß) 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-1ß, 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.

Key Words: fibrinolysis • malignancy • pleural effusion • proinflammatory cytokines • tuberculosis


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Activity of several hemostatic factors has been detected in pleural fluids.1 In patients with exudative pleural effusions, an increase in procoagulant activity, due mainly to tissue factors, has been observed.2 By and large, fibrin turnover is greatly affected by the activity of fibrinolysis. The formation of the key enzyme in fibrinolysis, plasmin, is based largely on the equilibrium between plasminogen activators and plasminogen activator inhibitors (PAIs).3

In patients with malignant pleural effusions, intrapleural administration of minocin, a tetracycline derivative, could induce pleural inflammation and fibrosis.4 A recent study5 indicated that the intrapleural injection of quinacrine, an irritative agent, in patients with malignant pleural effusions could increase the concentration of plasminogen inhibitor activator type I (PAI-1) and reduce the fibrinolytic activity in pleural fluid. In addition, the levels of proinflammatory cytokines as tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-1ß (IL-1ß) in pleural fluid appeared to be elevated markedly after the intrapleural injection of quinacrine in patients with malignant pleural effusions.6 7 These findings suggest a strong relationship between intrapleural fibrinolysis and proinflammatory cytokines.

The levels of TNF-{alpha} were reported to be significantly higher in tuberculous than in malignant pleural effusions.8 9 10 Increased levels of pleural fluid TNF-{alpha} appeared to be an important indicator in patients with pleural tuberculosis (TB) who might develop residual pleural thickening.11 A recent study12 indicated that pleural PAIs were greatly enhanced in exudates due to the inflammatory or infectious process, and plasminogen activators were increased in malignant effusions.

Taken together, these findings suggest that there is a considerable difference in intrapleural fibrinolysis between tuberculous and malignant pleural effusions, and the difference may be affected by proinflammatory cytokines, particularly TNF-{alpha}. In addition, the increased release of proinflammatory cytokines in pleural fluid caused by pleural TB may result in an imbalance of PAI-1 and tissue type plasminogen activator (tPA), which may subsequently lead to fibrin deposition and the development of residual pleural thickening.

This study was designed to evaluate the relationship between plasminogen activators, PAIs, and proinflammatory cytokines including TNF-{alpha} and IL-1ß in pleural fluid and peripheral blood in patients with tuberculous and malignant pleural effusions. In addition, the relationship between the concentrations of these parameters in pleural fluid and the development of residual pleural thickening in patients with tuberculous pleurisy was also examined.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Ninety-six consecutive patients with pleural effusions of unknown causes were hospitalized for diagnostic investigation. Pleural fluid was collected using a standard thoracocentesis technique immediately or within 24 h after hospitalization. Ten milliliters of venous blood were drawn simultaneously. The specimens were mixed with 3.8% sodium citrate solution in a ratio of 9:1 pleural fluid or blood to citrate. The sodium citrate-mixed pleural fluid and blood specimens were immersed separately in ice immediately and were then centrifuged at 1,200g for 5 min. The cell-free supernatants of pleural fluid and blood were frozen at - 70°C immediately after centrifuge for later examinations. Analyses of pleural fluids for total leukocytes, cell differentials of leukocytes, and the levels of protein, glucose, and lactate dehydrogenase (LDH) were performed. A pleural biopsy was performed after the collection of pleural fluid.

The patients were included subsequently if the examinations of pleural fluid and/or pleural biopsy specimens established a diagnosis of tuberculous or malignant pleural effusion. The patients were excluded if they had received any invasive procedures directed into the pleural cavity or if they had suffered chest trauma within 3 months prior to hospitalization. Thirty-three patients were proven to have tuberculous pleural effusion, as evidenced by growth of Mycobacterium tuberculosis from pleural fluid or by demonstration of granulomatous pleuritis on closed pleural biopsy specimen. After anti-TB chemotherapy, the resolution of pleural effusion and clinical symptoms was observed in all patients with tuberculous pleurisy. A diagnosis of malignant pleural effusion was established by demonstration of malignant cells in pleural fluid and/or on closed pleural biopsy specimen in 30 patients.

The levels of proinflammatory cytokines and fibrinolytic enzymes in the supernatants of pleural fluid and blood were measured by the commercially available enzyme-linked immunosorbent assay (ELISA) kits: tPA and PAI-1 (Diagnostic Stago; Asnieres-sur-seine; France), TNF-{alpha} (R & D System; Minneapolis, MN), and IL-1ß (T cell Diagnostics; Cambridge, MA). The levels of TNF-{alpha}, IL-1ß, tPA, and PAI-1 in blood and pleural fluid were measured in all patients. For concentrations that were below the lower limits detected by ELISA kits, the lower limits provided by the manufacturers were adapted as follows: PAI-1, 2.5 ng/mL; TNF-{alpha}, 4.4 pg/mL; and IL-1ß, 4.3 pg/mL.

Residual pleural thickening was measured as described before11 and defined as a pleural thickness of >= 10 mm shown on chest radiographs at the completion of anti-TB chemotherapy in the patients with tuberculous pleurisy.

Nonparametric tests were used to analyze pleural fluid variables since these variables were not normally distributed. Paired data comparisons were made using a Wilcoxon signed-rank test. Comparisons of the data between different groups were performed using a Mann-Whitney U test. The correlations between variables were determined by Spearman rank correlation coefficients.


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Pleural fluid characteristics, including total and differential counts of leukocytes, and the levels of LDH, glucose, and protein, are illustrated in Table 1 . These parameters were comparable between tuberculous and malignant effusions.


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  		Table 1. Pleural Fluid Characteristics Between Tuberculous and Malignant Pleural Effusions*

 
In the patients with tuberculous pleurisy, the levels of cytokines (TNF-{alpha} and IL-1ß) and fibrinolytic enzymes (tPA and PAI-1) were significantly higher in pleural fluid than in peripheral blood. Similar findings were observed in the patients with malignant pleural effusions (Table 2 ).


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  		Table 2. Pleural Fluid and Blood Levels of Proinflammatory Cytokines and Fibrinolytic Enzymes in the Patients With Tuberculous and Malignant Pleural Effusions*

 
Tuberculous pleural fluid had significantly higher levels of TNF-{alpha} than did malignant pleural fluid. Higher levels of IL-1ß were observed in tuberculous pleural fluid, but the difference did not reach statistical significance. The values of PAI-1 were significantly higher in tuberculous than in malignant pleural fluids. In contrast, the levels of tPA were significantly lower in tuberculous pleural fluid (Table 2) . There were no significant differences in blood levels of proinflammatory cytokines and fibrinolytic enzymes between the two groups (Table 2) .

In tuberculous pleural fluid, the levels of tPA correlated negatively with those of TNF-{alpha} and IL-1ß, and the values of PAI-1 and PAI-1/tPA ratios correlated positively with those of TNF-{alpha} and IL-1ß. In malignant pleural fluid, the levels of PAI-1 were positively correlated with those of TNF-{alpha} and IL-1ß (Table 3 ). There was no significant correlation between tPA and PAI-1 in both tuberculous and malignant pleural fluids.


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  		Table 3. Correlations Between Proinflammatory Cytokines and Fibrinolytic Enzymes in Tuberculous and Malignant Effusions

 
The levels of TNF-{alpha} were positively correlated with those of IL-1ß (r = 0.61; p < 0.01) in tuberculous pleural fluid. There was no significant correlation between the values of TNF-{alpha} and IL-1ß in malignant pleural fluid.

Residual pleural thickening was found in 9 of 33 patients (27.3%) with tuberculous pleurisy after completion of anti-TB chemotherapy. The pleural fluid of patients with residual pleural thickening had significantly higher levels of TNF{alpha}, IL-1ß, and PAI-1, and significantly lower values of tPA than the other patients (Table 4 ).


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  		Table 4. Pleural Fluid Levels of Proinflammatory Cytokines and Fibrinolytic Enzymes in Tuberculous Pleurisy Patients With or Without Residual Pleural Thickening*

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
A considerable difference in cytokine content has been reported between tuberculous and malignant pleural effusions. In agreement with previous reports, our results indicated that the levels of TNF-{alpha} were significantly higher in tuberculous than in malignant pleural fluids,8 9 10 but the levels of IL-1ß showed no significant difference.13 14 15

In in vitro studies, TNF-{alpha} and IL-1ß were demonstrated to have an effect on the release of PAI-1 and tPA by human mesothelial cells, and a synergetic effect exerted by these two cytokines was observed.16 17 Furthermore, significantly higher values of PAI-1 were found in exudative than in transudative effusions, particularly in the effusions caused by pleural inflammation, indicating that pleural inflammation may reduce fibrinolytic activity in pleural fluid via proinflammatory cytokines such as TNF-{alpha} and IL-1ß.12 18

In supporting this concept, our results showed that the levels of PAI-112 and TNF-{alpha}8 9 10 were significantly higher in tuberculous than in malignant pleural fluids. In contrast, the levels of tPA were significantly lower in tuberculous than in malignant effusions. In addition, we demonstrated that the levels of TNF-{alpha} were correlated positively with those of PAI-1 and the PAI-1/tPA ratio, and correlated negatively with those of tPA in tuberculous effusions. As for IL-1ß, our results showed that the values of IL-1ß were comparable between tuberculous and malignant pleural fluids. Nevertheless, the current study demonstrated that the levels of IL-1ß were correlated positively with those of TNF-{alpha}, PAI-1, and the PAI-1/tPA ratio, and correlated negatively with the levels of tPA (Table 3) . Accordingly, IL-1ß may have an auxiliary effect on fibrinolytic activity in tuberculous pleural fluid, although not as great as TNF-{alpha}.

In patients with malignant pleural effusions, the intrapleural administration of quinacrine could induce pleural inflammation and reduce pleural fibrinolytic activity, as evidenced by increased levels of PAI-1.5 6 7 The change of fibrinolytic activity in malignant pleural fluid after the intrapleural administration of irritative agents might be regulated by proinflammatory cytokines, since TNF-{alpha} and IL-1ß increased markedly in pleural fluid as did PAI-1.6 7 Taken together, these findings do support a relationship between inflammation, cytokines, and fibrinolysis in the pleural cavity. However, the cause of increased fibrinolytic activity as evidenced by higher levels of tPA in malignant pleural effusions remains to be determined.

The incidence of residual pleural thickening after anti-TB treatment varies from one study to another. It ranges from 10 to 52% or more.19 20 This variation can be attributed to the lack of a uniform concept of residual pleural thickening: some define a pleural thickening of >= 2 mm as abnormal, and others require a thickness >= 10 mm. In a recent study,11 higher levels of pleural fluid TNF-{alpha} appeared to be an important indicator in patients with pleural TB who might develop residual pleural thickening >= 10 mm. In agreement with the previous study, we found that the effusion levels of TNF-{alpha} and IL-1ß were significantly higher in tuberculous pleurisy patients with residual pleural thickening (Table 4) . In addition, significantly higher values of PAI-1 and significantly lower levels of tPA were also found in the patients with residual pleural thickening. This strongly suggests that proinflammatory cytokines such as TNF-{alpha} and IL-1ß, particularly TNF-{alpha}, do play an important role in regulating fibrinolytic activity and subsequent fibrin deposition in pleural space.

Although PAI-1 forms 1:1 covalent complexes with tPA,3 a negative correlation between pleural levels of PAI-1 and tPA was not observed in the present study. This may be due to the fact that immunoassays of tPA and PAI-1 measure both bound and free forms. This may explain the reason for the modest, but not highly significant, correlations between pleural fluid levels of PAI-1 and proinflammatory cytokines in the present study. However, pleural fluid PAI-1 levels detected by ELISA are highly correlated with pleural fluid PAI activities measured using the spectrolyse/fibrin functional assay.12 Accordingly, PAI-1 levels measured using ELISA can well reflect the PAI activity in pleural fluid.

In conclusion, compared to malignant pleural effusion, fibrinolytic activity appeared to be reduced in tuberculous pleural effusion. Pleural inflammation caused by TB may enhance the release of proinflammatory cytokines, particularly TNF-{alpha}, which may subsequently increase PAI-1 and decrease tPA levels in pleural fluid. The imbalance of PAI-1 and tPA in pleural space may lead to more fibrin deposition and the development of residual thickening in patients with tuberculous pleurisy.


   Footnotes
 
Abbreviations: ELISA = enzyme-linked immunosorbent assay; IL-1ß = interleukin-1ß; LDH = lactate dehydrogenase; PAI = plasminogen activator inhibitor; PAI-1 = plasminogen activator inhibitor type I; TB = tuberculosis; TNF-{alpha} = tumor necrosis factor-{alpha}; tPA = tissue type plasminogen activator

Supported by grants from the National Science Council of the Republic of China (NSC86–2314-B075–026) and Chang Gung Memorial Hospital (CMRP561).

Received for publication January 6, 1999. Accepted for publication May 27, 1999.


   References
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 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Glauser, FL, Otis, PT, Levine, RI, et al (1975) In vitro pleural fluid clottability and fibrinogen content. Chest 68,205-208[Abstract/Free Full Text]
  2. Idell, S, Girard, W, Koenig, KB, et al (1991) Abnormalities of passways of fibrin turnover in the human pleural space. Am Rev Respir Dis 144,187-194[ISI][Medline]
  3. Bithell, TC (1993) Blood coagulation. Lee, GR Bithell, TC Foerster, Jet al eds. Wintrobe‘s clinical hematology 9th ed. ,566-615 Lea & Febiger Philadelphia, PA.
  4. Sassoon, CSH, Light, RW, Vargas, FS, et al (1995) Temporal evolution of pleural fibrosis induced by intrapleural minocycline injection. Am J Respir Crit Care Med 151,791-794[Abstract]
  5. Agrenius, V, Chmielewska, J, Widström, O, et al (1989) Pleural fibrinolytic activity is decreased in inflammation as demonstrated in quinacrine pleurodesis treatment of malignant pleural effusion. Am Rev Respir Dis 140,1381-1385[ISI][Medline]
  6. Agrenius, V, Gustafsson, LE, Widström, O (1994) Tumor necrosis factor-{alpha} and nitric oxide, determined as nitrate, in malignant pleural effusion. Respir Med 88,743-748[CrossRef][ISI][Medline]
  7. Agrenius, V, Ukale, V, Widström, O, et al (1993) Quinarcine-induced pleural inflammation in malignant pleurisy: relation between drainage time of pleural fluid and local interleukin-1ß. Respiration 60,366-372[ISI][Medline]
  8. Gursel, G, Gokcora, N, Elbeg, S, et al (1995) Tumor necrosis factor-alpha (TNF-{alpha}) in pleural fluids. Tuber Lung Dis 76,370-371[CrossRef][ISI][Medline]
  9. Soderblom, T, Nyberg, P, Teppo, AM, et al (1996) Pleural fluid interferon-{gamma} and tumor necrosis factor-{alpha} in tuberculous and rheumatoid pleurisy. Eur Respir J 9,1652-1655[Abstract]
  10. Orphanidou, D, Gaga, M, Rasidakis, A, et al (1996) Tumor necrosis factor, interleukin-1 and adenosine deaminase in tuberculous pleural effusion. Respir Med 90,95-98[CrossRef][ISI][Medline]
  11. de Pablo, A, Villena, V, Echave-Sustaeta, J, et al (1997) Are pleural fluid parameters related to the development of residual pleural thickening in tuberculosis? Chest 112,1293-1297[Abstract/Free Full Text]
  12. Philip-Joët, F, Alessi, MC, Philip-Joët, C, et al (1995) Fibrinolytic and inflammatory processes in pleural effusions. Eur Respir J 8,1352-1356[Abstract]
  13. Shimokata, K, Saka, H, Murate, T, et al (1991) Cytokine content in pleural effusion: comparison between tuberculous and carcinomatous pleurisy. Chest 99,1103-1107[Abstract/Free Full Text]
  14. Silva-Mejias, C, Gamboa-Antinolo, F, Lopez-Cortes, LF, et al (1995) Interleukin-1ß in pleural fluids of differential diagnosis: its role as inflammatory mediator in empyema. Chest 108,942-945[Abstract/Free Full Text]
  15. Yanagawa, H, Yano, S, Haku, T, et al (1996) Interleukin-1 receptor and in pleural effusion due to inflammatory and malignant disease. Eur Respir J 9,1211-1216[Abstract]
  16. Idell, S, Zweib, C, Kumar, A, et al (1992) Pathways of fibrin turnover of human pleural mesothelial cells in vitro. Am J Respir Cell Mol Biol 7,414-426
  17. Whawell, SA, Thompson, JN (1995) Cytokine-induced release of plasminogen activator inhibitor-1 by human mesothelial cells. Eur J Surg 161,315-317[ISI][Medline]
  18. Idell, S, Girard, W, Koenig, KB, et al (1991) Abnormalities of pathways of fibrin turnover in human pleural space. Am Rev Respir Dis 144,187-194
  19. Lee, CH, Wang, WJ, Lan, RS, et al (1988) Corticosteroids in the treatment of tuberculous pleurisy. Chest 94,1256-1259[Abstract/Free Full Text]
  20. Barbas, CS, Cukier, A, Varvalho, CR, et al (1991) The relationship between pleural fluid findings and the development of pleural thickening in patients with pleural tuberculosis. Chest 100,1264-1267[Abstract/Free Full Text]



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